Novel compounds

ABSTRACT

Polypeptides and polynucleotides of the genes set forth in Table I and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing polypeptides and polynucleotides of the genes set forth in Table I in diagnostic assays.

FIELD OF INVENTION

[0001] This invention relates to newly identified polypeptides andpolynucleotides encoding such polypeptides, to their use in diagnosisand in identifying compounds that may be agonists, antagonists that arepotentially useful in therapy, and to production of such polypeptidesand polynucleotides. The polynucleotides and polypeptides of the presentinvention also relate to proteins with signal sequences which allow themto be secreted extracellularly or membrane-associated (hereinafter oftenreferred collectively as secreted proteins or secreted polypeptides).

BACKGROUND OF THE INVENTION

[0002] The drug discovery process is currently undergoing a fundamentalrevolution as it embraces “functional genomics”, that is, highthroughput genome- or gene-based biology. This approach as a means toidentify genes and gene products as therapeutic targets is rapidlysuperseding earlier approaches based on “positional cloning”. Aphenotype, that is a biological function or genetic disease, would beidentified and this would then be tracked back to the responsible gene,based on its genetic map position.

[0003] Functional genomics relies heavily on high-throughput DNAsequencing technologies and the various tools of bioinformatics toidentify gene sequences of potential interest from the many molecularbiology databases now available. There is a continuing need to identifyand characterise further genes and their related polypeptides/proteins,as targets for drug discovery.

[0004] Proteins and polypeptides that are naturally secreted into blood,lymph and other body fluids, or secreted into the cellular membrane areof primary interest for pharmaceutical research and development. Thereason for this interest is the relative ease to target proteintherapeutics into their place of action (body fluids or the cellularmembrane). The natural pathway for protein secretion into extracellularspace is the endoplasmic reticulum in eukaryotes and the inner membranein prokaryotes (Palade, 1975, Science, 189, 347; Milstein, Brownlee,Harrison, and Mathews, 1972, Nature New Biol., 239, 117; Blobel, andDobberstein, 1975, J. Cell. Biol., 67, 835). On the other hand, there isno known natural pathway for exporting a protein from the exterior ofthe cells into the cytosol (with the exception of pinocytosis, amechanism of snake venom toxin intrusion into cells). Thereforetargeting protein therapeutics into cells poses extreme difficulties.

[0005] The secreted and membrane-associated proteins include but are notlimited to all peptide hormones and their receptors (including but notlimited to insulin, growth hormones, chemokines, cytokines,neuropeptides, integrins, kallikreins, lamins, melanins, natriuretichormones, neuropsin, neurotropins, pituitiary hormones, pleiotropins,prostaglandins, secretogranins, selecting, thromboglobulins, thymosins),the breast and colon cancer gene products, leptin, the obesity geneprotein and its receptors, serum albumin, superoxide dismutase,spliceosome proteins, 7TM (transmembrane) proteins also called asG-protein coupled receptors, immunoglobulins, several families of serineproteinases (including but not limited to proteins of the bloodcoagulation cascade, digestive enzymes), deoxyribonuclease I, etc.

[0006] Therapeutics based on secreted or membrane-associated proteinsapproved by FDA or foreign agencies include but are not limited toinsulin, glucagon, growth hormone, chorionic gonadotropin, folliclestimulating hormone, luteinizing hormone, calcitonin,adrenocorticotropic hormone (ACTH), vasopressin, interleukines,interferones, immunoglobulins, lactoferrin (diverse products marketed byseveral companies), tissue-type plasminogen activator (Alteplase byGenentech), hyaulorindase (Wydase by Wyeth-Ayerst), dornase alpha(Pulmozyme\ by Genentech), Chymodiactin (chymopapain by Knoll),alglucerase (Ceredase by Genzyme), streptokinase (Kabikinase byPharmacia) (Streptase by Astra), etc. This indicates that secreted andmembrane-associated proteins have an established, proven history astherapeutic targets. Clearly, there is a need for identification andcharacterization of further secreted and membrane-associated proteinswhich can play a role in preventing, ameliorating or correctingdysfunction or disease, including but not limited to diabetes, breast-,prostate-, colon cancer and other malignant tumors, hyper- andhypotension, obesity, bulimia, anorexia, growth abnormalities, asthma,manic depression, dementia, delirium, mental retardation, Huntington'sdisease, Tourette's syndrome, schizophrenia, growth, mental or sexualdevelopment disorders, and dysfunctions of the blood cascade systemincluding those leading to stroke. The proteins of the present inventionwhich include the signal sequences are also useful to further elucidatethe mechanism of protein transport which at present is not entirelyunderstood, and thus can be used as research tools.

SUMMARY OF THE INVENTION

[0007] The present invention relates to particular polypeptides andpolynucleotides of the genes set forth in Table I, including recombinantmaterials and methods for their production. Such polypeptides andpolynucleotides are of interest in relation to methods of treatment ofcertain diseases, including, but not limited to, the diseases set forthin Tables III and V, hereinafter referred to as “diseases of theinvention”. In a further aspect, the invention relates to methods foridentifying agonists and antagonists (e.g., inhibitors) using thematerials provided by the invention, and treating conditions associatedwith imbalance of polypeptides and/or polynucleotides of the genes setforth in Table I with the identified compounds. In still a furtheraspect, the invention relates to diagnostic assays for detectingdiseases associated with inappropriate activity or levels the genes setforth in Table I. Another aspect of the invention concerns apolynucleotide comprising any of the nucleotide sequences set forth inthe Sequence Listing and a polypeptide comprising a polypeptide encodedby the nucleotide sequence. In another aspect, the invention relates toa polypeptide comprising any of the polypeptide sequences set forth inthe Sequence Listing and recombinant materials and methods for theirproduction. Another aspect of the invention relates to methods for usingsuch polypeptides and polynucleotides. Such uses include the treatmentof diseases, abnormalities and disorders (hereinafter simply referred toas diseases) caused by abnormal expression, production, function and ormetabolism of the genes of this invention, and such diseases are readilyapparent by those skilled in the art from the homology to other proteinsdisclosed for each attached sequence. In still another aspect, theinvention relates to methods to identify agonists and antagonists usingthe materials provided by the invention, and treating conditionsassociated with the imbalance with the identified compounds. Yet anotheraspect of the invention relates to diagnostic assays for detectingdiseases associated with inappropriate activity or levels of thesecreted proteins of the present invention.

DESCRIPTION OF THE INVENTION

[0008] In a first aspect, the present invention relates to polypeptidesthe genes set forth in Table I. Such polypeptides include:

[0009] (a) an isolated polypeptide encoded by a polynucleotidecomprising a sequence set forth in the Sequence Listing, herein whenreferring to polynucleotides or polypeptides of the Sequence Listing, areference is also made to the Sequence Listing referred to in theSequence Listing;

[0010] (b) an isolated polypeptide comprising a polypeptide sequencehaving at least 95%, 96%, 97%, 98%, or 99% identity to a polypeptidesequence set forth in the Sequence Listing;

[0011] (c) an isolated polypeptide comprising a polypeptide sequence setforth in the Sequence Listing;

[0012] (d) an isolated polypeptide having at least 95%, 96%, 97%, 98%,or 99% identity to a polypeptide sequence set forth in the SequenceListing;

[0013] (e) a polypeptide sequence set forth in the Sequence Listing; and

[0014] (f) an isolated polypeptide having or comprising a polypeptidesequence that has an Identity Index of 0.95, 0.96, 0.97, 0.98, or 0.99compared to a polypeptide sequence set forth in the Sequence Listing;

[0015] (g) fragments and variants of such polypeptides in (a) to (f).

[0016] Polypeptides of the present invention are believed to be membersof the gene families set forth in Table II. They are therefore oftherapeutic and diagnostic interest for the reasons set forth in TablesIII and V. The biological properties of the polypeptides andpolynucleotides of the genes set forth in Table I are hereinafterreferred to as “the biological activity” of polypeptides andpolynucleotides of the genes set forth in Table I. Preferably, apolypeptide of the present invention exhibits at least one biologicalactivity of the genes set forth in Table I.

[0017] Polypeptides of the present invention also include variants ofthe aforementioned polypeptides, including all allelic forms and splicevariants. Such polypeptides vary from the reference polypeptide byinsertions, deletions, and substitutions that may be conservative ornon-conservative, or any combination thereof. Particularly preferredvariants are those in which several, for instance from 50 to 30, from 30to 20, from 20 to 10, from 10 to 5, from 5 to 3, from 3 to 2, from 2 to1 or I amino acids are inserted, substituted or deleted, in anycombination.

[0018] Preferred fragments of polypeptides of the present inventioninclude an isolated polypeptide comprising an amino acid sequence havingat least 30, 50 or 100 contiguous amino acids from an amino acidsequence set forth in the Sequence Listing, or an isolated polypeptidecomprising an amino acid sequence having at least 30, 50 or 100contiguous amino acids truncated or deleted from an amino acid sequenceset forth in the Sequence Listing. Preferred fragments are biologicallyactive fragments that mediate the biological activity of polypeptidesand polynucleotides of the genes set forth in Table I, including thosewith a similar activity or an improved activity, or with a decreasedundesirable activity. Also preferred are those fragments that areantigenic or immunogenic in an animal, especially in a human.

[0019] Fragments of a polypeptide of the invention may be employed forproducing the corresponding full-length polypeptide by peptidesynthesis; therefore, these variants may be employed as intermediatesfor producing the full-length polypeptides of the invention. Apolypeptide of the present invention may be in the form of the “mature”protein or may be a part of a larger protein such as a precursor or afusion protein. It is often advantageous to include an additional aminoacid sequence that contains secretory or leader sequences,pro-sequences, sequences that aid in purification, for instance multiplehistidine residues, or an additional sequence for stability duringrecombinant production.

[0020] Polypeptides of the present invention can be prepared in anysuitable manner, for instance by isolation form naturally occurringsources, from genetically engineered host cells comprising expressionsystems (vide infra) or by chemical synthesis, using for instanceautomated peptide synthesizers, or a combination of such methods. Meansfor preparing such polypeptides are well understood in the art.

[0021] In a further aspect, the present invention relates topolynucleotides of the genes set forth in Table I. Such polynucleotidesinclude:

[0022] (a) an isolated polynucleotide comprising a polynucleotidesequence having at least 95%, 96%, 97%, 98%, or 99% identity to apolynucleotide sequence set forth in the Sequence Listing;

[0023] (b) an isolated polynucleotide comprising a polynucleotide setforth in the Sequence Listing;

[0024] (c) an isolated polynucleotide having at least 95%, 96%, 97%,98%, or 99% identity to a polynucleotide set forth in the SequenceListing;

[0025] (d) an isolated polynucleotide set forth in the Sequence Listing;

[0026] (e) an isolated polynucleotide comprising a polynucleotidesequence encoding a polypeptide sequence having at least 95%, 96%, 97%,98%, or 99% identity to a polypeptide sequence set forth in the SequenceListing;

[0027] (f) an isolated polynucleotide comprising a polynucleotidesequence encoding a polypeptide set forth in the Sequence Listing;

[0028] (g) an isolated polynucleotide having a polynucleotide sequenceencoding a polypeptide sequence having at least 95%, 96%, 97%, 98%, or99% identity to a polypeptide sequence set forth in the SequenceListing;

[0029] (h) an isolated polynucleotide encoding a polypeptide set forthin the Sequence Listing;

[0030] (i) an isolated polynucleotide having or comprising apolynucleotide sequence that has an Identity Index of 0.95, 0.96, 0.97,0.98, or 0.99 compared to a polynucleotide sequence set forth in theSequence Listing;

[0031] (j) an isolated polynucleotide having or comprising apolynucleotide sequence encoding a polypeptide sequence that has anIdentity Index of 0.95, 0.96, 0.97, 0.98, or 0.99 compared to apolypeptide sequence set forth in the Sequence Listing; and

[0032] polynucleotides that are fragments and variants of the abovementioned polynucleotides or that are complementary to above mentionedpolynucleotides, over the entire length thereof.

[0033] Preferred fragments of polynucleotides of the present inventioninclude an isolated polynucleotide comprising an nucleotide sequencehaving at least 15, 30, 50 or 100 contiguous nucleotides from a sequenceset forth in the Sequence Listing, or an isolated polynucleotidecomprising a sequence having at least 30, 50 or 100 contiguousnucleotides truncated or deleted from a sequence set forth in theSequence Listing.

[0034] Preferred variants of polynucleotides of the present inventioninclude splice variants, allelic variants, and polymorphisms, includingpolynucleotides having one or more single nucleotide polymorphisms(SNPs).

[0035] Polynucleotides of the present invention also includepolynucleotides encoding polypeptide variants that comprise an aminoacid sequence set forth in the Sequence Listing and in which several,for instance from 50 to 30, from 30 to 20, from 20 to 10, from 10 to 5,from 5 to 3, from 3 to 2, from 2 to 1 or 1 amino acid residues aresubstituted, deleted or added, in any combination.

[0036] In a further aspect, the present invention providespolynucleotides that are RNA transcripts of the DNA sequences of thepresent invention. Accordingly, there is provided an RNA polynucleotidethat:

[0037] (a) comprises an RNA transcript of the DNA sequence encoding apolypeptide set forth in the Sequence Listing;

[0038] (b) is a RNA transcript of a DNA sequence encoding a polypeptideset forth in the Sequence Listing;

[0039] (c) comprises an RNA transcript of a DNA sequence set forth inthe Sequence Listing; or

[0040] (d) is a RNA transcript of a DNA sequence set forth in theSequence Listing; and RNA polynucleotides that are complementarythereto.

[0041] The polynucleotide sequences set forth in the Sequence Listingshow homology with the polynucleotide sequences set forth in Table II. Apolynucleotide sequence set forth in the Sequence Listing is a cDNAsequence that encodes a polypeptide set forth in the Sequence Listing. Apolynucleotide sequence encoding a polypeptide set forth in the SequenceListing may be identical to a polypeptide encoding a sequence set forthin the Sequence Listing or it may be a sequence other than a sequenceset forth in the Sequence Listing, which, as a result of the redundancy(degeneracy) of the genetic code, also encodes a polypeptide set forthin the Sequence Listing. A polypeptide of a sequence set forth in theSequence Listing is related to other proteins of the gene families setforth in Table II, having homology and/or structural similarity with thepolypeptides set forth in Table II. Preferred polypeptides andpolynucleotides of the present invention are expected to have, interalia, similar biological functions/properties to their homologouspolypeptides and polynucleotides. Furthermore, preferred polypeptidesand polynucleotides of the present invention have at least one activityof the genes set forth in Table I.

[0042] Polynucleotides of the present invention may be obtained usingstandard cloning and screening techniques from a cDNA library derivedfrom mRNA from the tissues set forth in Table IV (see for instance,Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Ed., ColdSpring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989)).Polynucleotides of the invention can also be obtained from naturalsources such as genomic DNA libraries or can be synthesized using wellknown and commercially available techniques.

[0043] When polynucleotides of the present invention are used for therecombinant production of polypeptides of the present invention, thepolynucleotide may include the coding sequence for the maturepolypeptide, by itself, or the coding sequence for the maturepolypeptide in reading frame with other coding sequences, such as thoseencoding a leader or secretory sequence, a pre-, or pro- or prepro-protein sequence, or other fusion peptide portions. For example, amarker sequence that facilitates purification of the fused polypeptidecan be encoded. In certain preferred embodiments of this aspect of theinvention, the marker sequence is a hexa-histidine peptide, as providedin the pQE vector (Qiagen, Inc.) and described in Gentz et al., ProcNatl Acad Sci USA (1989) 86:821-824, or is an HA tag. A polynucleotidemay also contain non-coding 5′ and 3′ sequences, such as transcribed,non-translated sequences, splicing and polyadenylation signals, ribosomebinding sites and sequences that stabilize mRNA.

[0044] Polynucleotides that are identical, or have sufficient identityto a polynucleotide sequence set forth in the Sequence Listing, may beused as hybridization probes for cDNA and genomic DNA or as primers fora nucleic acid amplification reaction (for instance, PCR). Such probesand primers may be used to isolate full-length cDNAs and genomic clonesencoding polypeptides of the present invention and to isolate cDNA andgenomic clones of other genes (including genes encoding paralogs fromhuman sources and orthologs and paralogs from other species) that have ahigh sequence similarity to sequences set forth in the Sequence Listing,typically at least 95% identity. Preferred probes and primers willgenerally comprise at least 15 nucleotides, preferably, at least 30nucleotides and may have at least 50, if not at least 100 nucleotides.Particularly preferred probes will have between 30 and 50 nucleotides.Particularly preferred primers will have between 20 and 25 nucleotides.

[0045] A polynucleotide encoding a polypeptide of the present invention,including homologs from other species, may be obtained by a processcomprising the steps of screening a library under stringenthybridization conditions with a labeled probe having a sequence setforth in the Sequence Listing or a fragment thereof, preferably of atleast 15 nucleotides; and isolating full-length cDNA and genomic clonescontaining the polynucleotide sequence set forth in the SequenceListing. Such hybridization techniques are well known to the skilledartisan. Preferred stringent hybridization conditions include overnightincubation at 42° C. in a solution comprising: 50% formamide, 5×SSC (150mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5×Denhardt's solution, 10% dextran sulfate, and 20 microgram/ml denatured,sheared salmon sperm DNA; followed by washing the filters in 0.1×SSC atabout 65° C. Thus the present invention also includes isolatedpolynucleotides, preferably with a nucleotide sequence of at least 100,obtained by screening a library under stringent hybridization conditionswith a labeled probe having the sequence set forth in the SequenceListing or a fragment thereof, preferably of at least 15 nucleotides.

[0046] The skilled artisan will appreciate that, in many cases, anisolated cDNA sequence will be incomplete, in that the region coding forthe polypeptide does not extend all the way through to the 5′ terminus.This is a consequence of reverse transcriptase, an enzyme withinherently low “processivity” (a measure of the ability of the enzyme toremain attached to the template during the polymerisation reaction),failing to complete a DNA copy of the mRNA template during first strandcDNA synthesis.

[0047] There are several methods available and well known to thoseskilled in the art to obtain full-length cDNAs, or extend short cDNAs,for example those based on the method of Rapid Amplification of cDNAends (RACE) (see, for example, Frohman et al., Proc Nat Acad Sci USA 85,8998-9002, 1988). Recent modifications of the technique, exemplified bythe Marathon (trade mark) technology (Clontech Laboratories Inc.) forexample, have significantly simplified the search for longer cDNAs. Inthe Marathon (trade mark) technology, cDNAs have been prepared from mRNAextracted from a chosen tissue and an ‘adaptor’ sequence ligated ontoeach end. Nucleic acid amplification (PCR) is then carried out toamplify the “missing” 5′ end of the cDNA using a combination of genespecific and adaptor specific oligonucleotide primers. The PCR reactionis then repeated using ‘nested’ primers, that is, primers designed toanneal within the amplified product (typically an adapter specificprimer that anneals further 3′ in the adaptor sequence and a genespecific primer that anneals further 5′ in the known gene sequence). Theproducts of this reaction can then be analyzed by DNA sequencing and afull-length cDNA constructed either by joining the product directly tothe existing cDNA to give a complete sequence, or carrying out aseparate full-length PCR using the new sequence information for thedesign of the 5′ primer.

[0048] Recombinant polypeptides of the present invention may be preparedby processes well known in the art from genetically engineered hostcells comprising expression systems. Accordingly, in a further aspect,the present invention relates to expression systems comprising apolynucleotide or polynucleotides of the present invention, to hostcells which are genetically engineered with such expression systems andto the production of polypeptides of the invention by recombinanttechniques. Cell-free translation systems can also be employed toproduce such proteins using RNAs derived from the DNA constructs of thepresent invention.

[0049] For recombinant production, host cells can be geneticallyengineered to incorporate expression systems or portions thereof forpolynucleotides of the present invention. Polynucleotides may beintroduced into host cells by methods described in many standardlaboratory manuals, such as Davis et al., Basic Methods in MolecularBiology (1986) and Sambrook et al.(ibid). Preferred methods ofintroducing polynucleotides into host cells include, for instance,calcium phosphate transfection, DEAE-dextran mediated transfection,transvection, micro-injection, cationic lipid-mediated transfection,electroporation, transduction, scrape loading, ballistic introduction orinfection.

[0050] Representative examples of appropriate hosts include bacterialcells, such as Streptococci, Staphylococci, E. coli, Streptomyces andBacillus subtilis cells; fungal cells, such as yeast cells andAspergillus cells; insect cells such as Drosophila S2 and Spodoptera Sf9cells; animal cells such as CHO, COS, HeLa, C127, 3T3, BHK, HEK 293 andBowes melanoma cells; and plant cells.

[0051] A great variety of expression systems can be used, for instance,chromosomal, episomal and virus-derived systems, e.g., vectors derivedfrom bacterial plasmids, from bacteriophage, from transposons, fromyeast episomes, from insertion elements, from yeast chromosomalelements, from viruses such as baculoviruses, papova viruses, such asSV40, vaccinia viruses, adenoviruses, fowl pox viruses, pseudorabiesviruses and retroviruses, and vectors derived from combinations thereof,such as those derived from plasmid and bacteriophage genetic elements,such as cosmids and phagemids. The expression systems may containcontrol regions that regulate as well as engender expression. Generally,any system or vector that is able to maintain, propagate or express apolynucleotide to produce a polypeptide in a host may be used. Theappropriate polynucleotide sequence may be inserted into an expressionsystem by any of a variety of well-known and routine techniques, suchas, for example, those set forth in Sambrook et al., (ibid). Appropriatesecretion signals may be incorporated into the desired polypeptide toallow secretion of the translated protein into the lumen of theendoplasmic reticulum, the periplasmic space or the extracellularenvironment. These signals may be endogenous to the polypeptide or theymay be heterologous signals.

[0052] If a polypeptide of the present invention is to be expressed foruse in screening assays, it is generally preferred that the polypeptidebe produced at the surface of the cell. In this event, the cells may beharvested prior to use in the screening assay. If the polypeptide issecreted into the medium, the medium can be recovered in order torecover and purify the polypeptide. If produced intracellularly, thecells must first be lysed before the polypeptide is recovered.

[0053] Polypeptides of the present invention can be recovered andpurified from recombinant cell cultures by well-known methods includingammonium sulfate or ethanol precipitation, acid extraction, anion orcation exchange chromatography, phosphocellulose chromatography,hydrophobic interaction chromatography, affinity chromatography,hydroxylapatite chromatography and lectin chromatography. Mostpreferably, high performance liquid chromatography is employed forpurification. Well known techniques for refolding proteins may beemployed to regenerate active conformation when the polypeptide isdenatured during intracellular synthesis, isolation and/or purification.

[0054] Polynucleotides of the present invention may be used asdiagnostic reagents, through detecting mutations in the associated gene.Detection of a mutated form of a gene is characterized by thepolynucleotides set forth in the Sequence Listing in the cDNA or genomicsequence and which is associated with a dysfunction. Will provide adiagnostic tool that can add to, or define, a diagnosis of a disease, orsusceptibility to a disease, which results from under-expression,over-expression or altered spatial or temporal expression of the gene.Individuals carrying mutations in the gene may be detected at the DNAlevel by a variety of techniques well known in the art.

[0055] Nucleic acids for diagnosis may be obtained from a subject'scells, such as from blood, urine, saliva, tissue biopsy or autopsymaterial. The genomic DNA may be used directly for detection or it maybe amplified enzymatically by using PCR, preferably RT-PCR, or otheramplification techniques prior to analysis. RNA or cDNA may also be usedin similar fashion. Deletions and insertions can be detected by a changein size of the amplified product in comparison to the normal genotype.Point mutations can be identified by hybridizing amplified DNA tolabeled nucleotide sequences of the genes set forth in Table I.Perfectly matched sequences can be distinguished from mismatchedduplexes by RNase digestion or by differences in melting temperatures.DNA sequence difference may also be detected by alterations in theelectrophoretic mobility of DNA fragments in gels, with or withoutdenaturing agents, or by direct DNA sequencing (see, for instance, Myerset al., Science (1985) 230:1242). Sequence changes at specific locationsmay also be revealed by nuclease protection assays, such as RNase and S1protection or the chemical cleavage method (see Cotton et al., Proc NatlAcad Sci USA (1985) 85: 4397-4401).

[0056] An array of oligonucleotides probes comprising polynucleotidesequences or fragments thereof of the genes set forth in Table I can beconstructed to conduct efficient screening of e.g., genetic mutations.Such arrays are preferably high density arrays or grids. Arraytechnology methods are well known and have general applicability and canbe used to address a variety of questions in molecular geneticsincluding gene expression, genetic linkage, and genetic variability,see, for example, M. Chee et al., Science, 274, 610-613 (1996) and otherreferences cited therein.

[0057] Detection of abnormally decreased or increased levels ofpolypeptide or mRNA expression may also be used for diagnosing ordetermining susceptibility of a subject to a disease of the invention.Decreased or increased expression can be measured at the RNA level usingany of the methods well known in the art for the quantitation ofpolynucleotides, such as, for example, nucleic acid amplification, forinstance PCR, RT-PCR, RNase protection, Northern blotting and otherhybridization methods. Assay techniques that can be used to determinelevels of a protein, such as a polypeptide of the present invention, ina sample derived from a host are well-known to those of skill in theart. Such assay methods include radio-immunoassays, competitive-bindingassays, Western Blot analysis and ELISA assays.

[0058] Thus in another aspect, the present invention relates to adiagnostic kit comprising:

[0059] (a) a polynucleotide of the present invention, preferably thenucleotide sequence set forth in the Sequence Listing, or a fragment oran RNA transcript thereof;

[0060] (b) a nucleotide sequence complementary to that of (a);

[0061] (c) a polypeptide of the present invention, preferably thepolypeptide set forth in the Sequence Listing or a fragment thereof; or

[0062] (d) an antibody to a polypeptide of the present invention,preferably to the polypeptide set forth in the Sequence Listing.

[0063] It will be appreciated that in any such kit, (a), (b), (c) or (d)may comprise a substantial component. Such a kit will be of use indiagnosing a disease or susceptibility to a disease, particularlydiseases of the invention, amongst others.

[0064] The polynucleotide sequences of the present invention arevaluable for chromosome localisation studies. The sequences set forth inthe Sequence Listing are specifically targeted to, and can hybridizewith, a particular location on an individual human chromosome. Themapping of relevant sequences to chromosomes according to the presentinvention is an important first step in correlating those sequences withgene associated disease. Once a sequence has been mapped to a precisechromosomal location, the physical position of the sequence on thechromosome can be correlated with genetic map data. Such data are foundin, for example, V. McKusick, Mendelian Inheritance in Man (availableon-line through Johns Hopkins University Welch Medical Library). Therelationship between genes and diseases that have been mapped to thesame chromosomal region are then identified through linkage analysis(co-inheritance of physically adjacent genes). Precise human chromosomallocalisations for a genomic sequence (gene fragment etc.) can bedetermined using Radiation Hybrid (RH) Mapping (Walter, M. Spillett, D.,Thomas, P., Weissenbach, J., and Goodfellow, P., (1994) A method forconstructing radiation hybrid maps of whole genomes, Nature Genetics 7,22-28). A number of RH panels are available from Research Genetics(Huntsville, Ala., USA) e.g. the GeneBridge4 RH panel (Hum Mol Genet1996 March;5(3):339-46 A radiation hybrid map of the human genome.Gyapay G, Schnmitt K, Fizames C, Jones H, Vega-Czarny N, Spillett D,Muselet D, Prud'Homme J F, Dib C, Auffray C, Morissette J, WeissenbachJ, Goodfellow P N). To determine the chromosomal location of a geneusing this panel, 93 PCRs are performed using primers designed from thegene of interest on RH DNAs. Each of these DNAs contains random humangenomic fragments maintained in a hamster background (human/hamsterhybrid cell lines). These PCRs result in 93 scores indicating thepresence or absence of the PCR product of the gene of interest. Thesescores are compared with scores created using PCR products from genomicsequences of known location. This comparison is conducted athttp://www.genome.wi.mit.edu/.

[0065] The polynucleotide sequences of the present invention are alsovaluable tools for tissue expression studies. Such studies allow thedetermination of expression patterns of polynucleotides of the presentinvention which may give an indication as to the expression patterns ofthe encoded polypeptides in tissues, by detecting the mRNAs that encodethem. The techniques used are well known in the art and include in situhydridization techniques to clones arrayed on a grid, such as cDNAmicroarray hybridization (Schena et al, Science, 270, 467-470, 1995 andShalon et al, Genome Res, 6, 639-645, 1996) and nucleotide amplificationtechniques such as PCR. A preferred method uses the TAQMAN (Trade mark)technology available from Perkin Elmer. Results from these studies canprovide an indication of the normal function of the polypeptide in theorganism. In addition, comparative studies of the normal expressionpattern of mRNAs with that of mRNAs encoded by an alternative form ofthe same gene (for example, one having an alteration in polypeptidecoding potential or a regulatory mutation) can provide valuable insightsinto the role of the polypeptides of the present invention, or that ofinappropriate expression thereof in disease. Such inappropriateexpression may be of a temporal, spatial or simply quantitative nature.

[0066] A further aspect of the present invention relates to antibodies.The polypeptides of the invention or their fragments, or cellsexpressing them, can be used as immunogens to produce antibodies thatare immunospecific for polypeptides of the present invention. The term“immunospecific” means that the antibodies have substantially greateraffinity for the polypeptides of the invention than their affinity forother related polypeptides in the prior art.

[0067] Antibodies generated against polypeptides of the presentinvention may be obtained by administering the polypeptides orepitope-bearing fragments, or cells to an animal, preferably a non-humananimal, using routine protocols. For preparation of monoclonalantibodies, any technique which provides antibodies produced bycontinuous cell line cultures can be used. Examples include thehybridoma technique (Kohler, G. and Milstein, C., Nature (1975)256:495-497), the trioma technique, the human B-cell hybridoma technique(Kozbor et al., Immunology Today (1983) 4:72) and the EBV-hybridomatechnique (Cole et al., Monoclonal Antibodies and Cancer Therapy, 77-96,Alan R. Liss, Inc., 1985).

[0068] Techniques for the production of single chain antibodies, such asthose described in U.S. Pat. No. 4,946,778, can also be adapted toproduce single chain antibodies to polypeptides of this invention. Also,transgenic mice, or other organisms, including other mammals, may beused to express humanized antibodies.

[0069] The above-described antibodies may be employed to isolate or toidentify clones expressing the polypeptide or to purify the polypeptidesby affinity chromatography. Antibodies against polypeptides of thepresent invention may also be employed to treat diseases of theinvention, amongst others.

[0070] Polypeptides and polynucleotides of the present invention mayalso be used as vaccines. Accordingly, in a further aspect, the presentinvention relates to a method for inducing an immunological response ina mammal that comprises inoculating the mammal with a polypeptide of thepresent invention, adequate to produce antibody and/or T cell immuneresponse, including, for example, cytokine-producing T cells orcytotoxic T cells, to protect said animal from disease, whether thatdisease is already established within the individual or not. Animmunological response in a mammal may also be induced by a methodcomprises delivering a polypeptide of the present invention via a vectordirecting expression of the polynucleotide and coding for thepolypeptide in vivo in order to induce such an immunological response toproduce antibody to protect said animal from diseases of the invention.One way of administering the vector is by accelerating it into thedesired cells as a coating on particles or otherwise. Such nucleic acidvector may comprise DNA, RNA, a modified nucleic acid, or a DNA/RNAhybrid. For use a vaccine, a polypeptide or a nucleic acid vector willbe normally provided as a vaccine formulation (composition). Theformulation may further comprise a suitable carrier. Since a polypeptidemay be broken down in the stomach, it is preferably administeredparenterally (for instance, subcutaneous, intramuscular, intravenous, orintra-dermal injection). Formulations suitable for parenteraladministration include aqueous and non-aqueous sterile injectionsolutions that may contain anti-oxidants, buffers, bacteriostats andsolutes that render the formulation instonic with the blood of therecipient; and aqueous and non-aqueous sterile suspensions that mayinclude suspending agents or thickening agents. The formulations may bepresented in unit-dose or multi-dose containers, for example, sealedampoules and vials and may be stored in a freeze-dried conditionrequiring only the addition of the sterile liquid carrier immediatelyprior to use. The vaccine formulation may also include adjuvant systemsfor enhancing the immunogenicity of the formulation, such as oil-inwater systems and other systems known in the art. The dosage will dependon the specific activity of the vaccine and can be readily determined byroutine experimentation.

[0071] Polypeptides of the present invention have one or more biologicalfunctions that are of relevance in one or more disease states, inparticular the diseases of the invention hereinbefore mentioned. It istherefore useful to identify compounds that stimulate or inhibit thefunction or level of the polypeptide. Accordingly, in a further aspect,the present invention provides for a method of screening compounds toidentify those that stimulate or inhibit the function or level of thepolypeptide. Such methods identify agonists or antagonists that may beemployed for therapeutic and prophylactic purposes for such diseases ofthe invention as hereinbefore mentioned. Compounds may be identifiedfrom a variety of sources, for example, cells, cell-free preparations,chemical libraries, collections of chemical compounds, and naturalproduct mixtures. Such agonists or antagonists so-identified may benatural or modified substrates, ligands, receptors, enzymes, etc., asthe case may be, of the polypeptide; a structural or functional mimeticthereof (see Coligan et al., Current Protocols in Immunology1(2):Chapter 5 (1991)) or a small molecule. Such small moleculespreferably have a molecular weight below 2,000 daltons, more preferablybetween 300 and 1,000 daltons, and most preferably between 400 and 700daltons. It is preferred that these small molecules are organicmolecules.

[0072] The screening method may simply measure the binding of acandidate compound to the polypeptide, or to cells or membranes bearingthe polypeptide, or a fusion protein thereof, by means of a labeldirectly or indirectly associated with the candidate compound.Alternatively, the screening method may involve measuring or detecting(qualitatively or quantitatively) the competitive binding of a candidatecompound to the polypeptide against a labeled competitor (e.g. agonistor antagonist). Further, these screening methods may test whether thecandidate compound results in a signal generated by activation orinhibition of the polypeptide, using detection systems appropriate tothe cells bearing the polypeptide. Inhibitors of activation aregenerally assayed in the presence of a known agonist and the effect onactivation by the agonist by the presence of the candidate compound isobserved. Further, the screening methods may simply comprise the stepsof mixing a candidate compound with a solution containing a polypeptideof the present invention, to form a mixture, measuring an activity ofthe genes set forth in Table I in the mixture, and comparing activity ofthe mixture of the genes set forth in Table I to a control mixture whichcontains no candidate compound.

[0073] Polypeptides of the present invention may be employed inconventional low capacity screening methods and also in high-throughputscreening (HTS) formats. Such HTS formats include not only thewell-established use of 96- and, more recently, 384-well micotiterplates but also emerging methods such as the nanowell method describedby Schullek et al, Anal Biochem., 246, 20-29, (1997).

[0074] Fusion proteins, such as those made from Fc portion andpolypeptide of the genes set forth in Table I, as hereinbeforedescribed, can also be used for high-throughput screening assays toidentify antagonists for the polypeptide of the present invention (seeD. Bennett et al., J Mol Recognition, 8:52-58 (1995); and K. Johanson etal., J Biol Chem, 270(16):9459-9471 (1995)).

[0075] The polynucleotides, polypeptides and antibodies to thepolypeptide of the present invention may also be used to configurescreening methods for detecting the effect of added compounds on theproduction of mRNA and polypeptide in cells. For example, an ELISA assaymay be constructed for measuring secreted or cell associated levels ofpolypeptide using monoclonal and polyclonal antibodies by standardmethods known in the art. This can be used to discover agents that mayinhibit or enhance the production of polypeptide (also called antagonistor agonist, respectively) from suitably manipulated cells or tissues.

[0076] A polypeptide of the present invention may be used to identifymembrane bound or soluble receptors, if any, through standard receptorbinding techniques known in the art. These include, but are not limitedto, ligand binding and crosslinking assays in which the polypeptide islabeled with a radioactive isotope (for instance, ¹²⁵I), chemicallymodified (for instance, biotinylated), or fused to a peptide sequencesuitable for detection or purification, and incubated with a source ofthe putative receptor (cells, cell membranes, cell supernatants, tissueextracts, bodily fluids). Other methods include biophysical techniquessuch as surface plasmon resonance and spectroscopy. These screeningmethods may also be used to identify agonists and antagonists of thepolypeptide that compete with the binding of the polypeptide to itsreceptors, if any. Standard methods for conducting such assays are wellunderstood in the art.

[0077] Examples of antagonists of polypeptides of the present inventioninclude antibodies or, in some cases, oligonucleotides or proteins thatare closely related to the ligands, substrates, receptors, enzymes,etc., as the case may be, of the polypeptide, e.g., a fragment of theligands, substrates, receptors, enzymes, etc.; or a small molecule thatbind to the polypeptide of the present invention but do not elicit aresponse, so that the activity of the polypeptide is prevented.

[0078] Screening methods may also involve the use of transgenictechnology and the genes set forth in Table I. The art of constructingtransgenic animals is well established. For example, the genes set forthin Table I may be introduced through microinjection into the malepronucleus of fertilized oocytes, retroviral transfer into pre- orpost-implantation embryos, or injection of genetically modified, such asby electroporation, embryonic stem cells into host blastocysts.Particularly useful transgenic animals are so-called “knock-in” animalsin which an animal gene is replaced by the human equivalent within thegenome of that animal. Knock-in transgenic animals are useful in thedrug discovery process, for target validation, where the compound isspecific for the human target. Other useful transgenic animals areso-called “knock-out” animals in which the expression of the animalortholog of a polypeptide of the present invention and encoded by anendogenous DNA sequence in a cell is partially or completely annulled.The gene knock-out may be targeted to specific cells or tissues, mayoccur only in certain cells or tissues as a consequence of thelimitations of the technology, or may occur in all, or substantiallyall, cells in the animal. Transgenic animal technology also offers awhole animal expression-cloning system in which introduced genes areexpressed to give large amounts of polypeptides of the presentinvention.

[0079] Screening kits for use in the above described methods form afurther aspect of the present invention. Such screening kits comprise:

[0080] (a) a polypeptide of the present invention;

[0081] (b) a recombinant cell expressing a polypeptide of the presentinvention;

[0082] (c) a cell membrane expressing a polypeptide of the presentinvention; or

[0083] (d) an antibody to a polypeptide of the present invention;

[0084] which polypeptide is preferably that set forth in the SequenceListing.

[0085] It will be appreciated that in any such kit, (a), (b), (c) or (d)may comprise a substantial component.

[0086] Glossary

[0087] The following definitions are provided to facilitateunderstanding of certain terms used frequently hereinbefore.

[0088] “Antibodies” as used herein includes polyclonal and monoclonalantibodies, chimeric, single chain, and humanized antibodies, as well asFab fragments, including the products of an

[0089] Fab or other immunoglobulin expression library.

[0090] “Isolated” means altered “by the hand of man” from its naturalstate, i.e., if it occurs in nature, it has been changed or removed fromits original environment, or both. For example, a polynucleotide or apolypeptide naturally present in a living organism is not “isolated,”but the same polynucleotide or polypeptide separated from the coexistingmaterials of its natural state is “isolated”, as the term is employedherein. Moreover, a polynucleotide or polypeptide that is introducedinto an organism by transformation, genetic manipulation or by any otherrecombinant method is “isolated” even if it is still present in saidorganism, which organism may be living or non-living.

[0091] “Secreted protein activity or secreted polypeptide activity” or“biological activity of the secreted protein or secreted polypeptide”refers to the metabolic or physiologic function of said secreted proteinincluding similar activities or improved activities or these activitieswith decreased undesirable side-effects. Also included are antigenic andimmunogenic activities of said secreted protein.

[0092] “Secreted protein gene” refers to a polynucleotide comprising anyof the attached nucleotide sequences or allelic variants thereof and/ortheir complements.

[0093] “Polynucleotide” generally refers to any polyribonucleotide (RNA)or polydeoxribonucleotide (DNA), which may be unmodified or modified RNAor DNA. “Polynucleotides” include, without limitation, single- anddouble-stranded DNA, DNA that is a mixture of single- anddouble-stranded regions, single- and double-stranded RNA, and RNA thatis mixture of single- and double-stranded regions, hybrid moleculescomprising DNA and RNA that may be single-stranded or, more typically,double-stranded or a mixture of single- and double-stranded regions. Inaddition, “polynucleotide” refers to triple-stranded regions comprisingRNA or DNA or both RNA and DNA. The term “polynucleotide” also includesDNAs or RNAs containing one or more modified bases and DNAs or RNAs withbackbones modified for stability or for other reasons. “Modified” basesinclude, for example, tritylated bases and unusual bases such asinosine. A variety of modifications may be made to DNA and RNA; thus,“polynucleotide” embraces chemically, enzymatically or metabolicallymodified forms of polynucleotides as typically found in nature, as wellas the chemical forms of DNA and RNA characteristic of viruses andcells. “Polynucleotide” also embraces relatively short polynucleotides,often referred to as oligonucleotides.

[0094] “Polypeptide” refers to any polypeptide comprising two or moreamino acids joined to each other by peptide bonds or modified peptidebonds, i.e., peptide isosteres. “Polypeptide” refers to both shortchains, commonly referred to as peptides, oligopeptides or oligomers,and to longer chains, generally referred to as proteins. Polypeptidesmay contain amino acids other than the 20 gene-encoded amino acids.“Polypeptides” include amino acid sequences modified either by naturalprocesses, such as post-translational processing, or by chemicalmodification techniques that are well known in the art. Suchmodifications are well described in basic texts and in more detailedmonographs, as well as in a voluminous research literature.Modifications may occur anywhere in a polypeptide, including the peptidebackbone, the amino acid side-chains and the amino or carboxyl termini.It will be appreciated that the same type of modification may be presentto the same or varying degrees at several sites in a given polypeptide.Also, a given polypeptide may contain many types of modifications.Polypeptides may be branched as a result of ubiquitination, and they maybe cyclic, with or without branching. Cyclic, branched and branchedcyclic polypeptides may result from post-translation natural processesor may be made by synthetic methods. Modifications include acetylation,acylation, ADP-ribosylation, amidation, biotinylation, covalentattachment of flavin, covalent attachment of a heme moiety, covalentattachment of a nucleotide or nucleotide derivative, covalent attachmentof a lipid or lipid derivative, covalent attachment ofphosphotidylinositol, cross-linking, cyclization, disulfide bondformation, demethylation, formation of covalent cross-links, formationof cystine, formation of pyroglutamate, formylation,gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation,iodination, methylation, myristoylation, oxidation, proteolyticprocessing, phosphorylation, prenylation, racemization, selenoylation,sulfation, transfer-RNA mediated addition of amino acids to proteinssuch as arginylation, and ubiquitination (see, for instance,Proteins—Structure and Molecular Properties, 2nd Ed., T. E. Creighton,W. H. Freeman and Company, New York, 1993; Wold, F., Post-translationalProtein Modifications: Perspectives and Prospects, 1-12, inPost-translational Covalent Modification of Proteins, B. C. Johnson,Ed., Academic Press, New York, 1983; Seifter et al., “Analysis forprotein modifications and nonprotein cofactors”, Meth Enzymol, 182,626-646, 1990, and Rattan et al., “Protein Synthesis: Post-translationalModifications and Aging”, Ann NY Acad Sci, 663, 48-62, 1992).

[0095] “Fragment” of a polypeptide sequence refers to a polypeptidesequence that is shorter than the reference sequence but that retainsessentially the same biological function or activity as the referencepolypeptide. “Fragment” of a polynucleotide sequence refers to apolynucleotide sequence that is shorter than the reference sequence setforth in the Sequence Listing.

[0096] “Variant” refers to a polynucleotide or polypeptide that differsfrom a reference polynucleotide or polypeptide, but retains theessential properties thereof. A typical variant of a polynucleotidediffers in nucleotide sequence from the reference polynucleotide.Changes in the nucleotide sequence of the variant may or may not alterthe amino acid sequence of a polypeptide encoded by the referencepolynucleotide. Nucleotide changes may result in amino acidsubstitutions, additions, deletions, fusions and truncations in thepolypeptide encoded by the reference sequence, as discussed below. Atypical variant of a polypeptide differs in amino acid sequence from thereference polypeptide. Generally, alterations are limited so that thesequences of the reference polypeptide and the variant are closelysimilar overall and, in many regions, identical. A variant and referencepolypeptide may differ in amino acid sequence by one or moresubstitutions, insertions, deletions in any combination. A substitutedor inserted amino acid residue may or may not be one encoded by thegenetic code. Typical conservative substitutions include Gly, Ala; Val,Ile, Leu; Asp, Glu; Asn, Gln; Ser, Thr; Lys, Arg; and Phe and Tyr. Avariant of a polynucleotide or polypeptide may be naturally occurringsuch as an allele, or it may be a variant that is not known to occurnaturally. Non-naturally occurring variants of polynucleotides andpolypeptides may be made by mutagenesis techniques or by directsynthesis. Also included as variants are polypeptides having one or morepost-translational modifications, for instance glycosylation,phosphorylation, methylation, ADP ribosylation and the like. Embodimentsinclude methylation of the N-terminal amino acid, phosphorylations ofserines and threonines and modification of C-terminal glycines.

[0097] “Allele” refers to one of two or more alternative forms of a geneoccurring at a given locus in the genome.

[0098] “Polymorphism” refers to a variation in nucleotide sequence (andencoded polypeptide sequence, if relevant) at a given position in thegenome within a population.

[0099] “Single Nucleotide Polymorphism” (SNP) refers to the occurrenceof nucleotide variability at a single nucleotide position in the genome,within a population. An SNP may occur within a gene or within intergenicregions of the genome. SNPs can be assayed using Allele SpecificAmplification (ASA). For the process at least 3 primers are required. Acommon primer is used in reverse complement to the polymorphism beingassayed. This common primer can be between 50 and 1500 bps from thepolymorphic base. The other two (or more) primers are identical to eachother except that the final 3′ base wobbles to match one of the two (ormore) alleles that make up the polymorphism. Two (or more) PCR reactionsare then conducted on sample DNA, each using the common primer and oneof the Allele Specific Primers.

[0100] “Splice Variant” as used herein refers to cDNA molecules producedfrom RNA molecules initially transcribed from the same genomic DNAsequence but which have undergone alternative RNA splicing. AlternativeRNA splicing occurs when a primary RNA transcript undergoes splicing,generally for the removal of introns, which results in the production ofmore than one mRNA molecule each of that may encode different amino acidsequences. The term splice variant also refers to the proteins encodedby the above cDNA molecules.

[0101] “Identity” reflects a relationship between two or morepolypeptide sequences or two or more polynucleotide sequences,determined by comparing the sequences. In general, identity refers to anexact nucleotide to nucleotide or amino acid to amino acidcorrespondence of the two polynucleotide or two polypeptide sequences,respectively, over the length of the sequences being compared.

[0102] “% Identity”—For sequences where there is not an exactcorrespondence, a “% identity” may be determined. In general, the twosequences to be compared are aligned to give a maximum correlationbetween the sequences. This may include inserting “gaps” in either oneor both sequences, to enhance the degree of alignment. A % identity maybe determined over the whole length of each of the sequences beingcompared (so-called global alignment), that is particularly suitable forsequences of the same or very similar length, or over shorter, definedlengths (so-called local alignment), that is more suitable for sequencesof unequal length.

[0103] “Similarity” is a further, more sophisticated measure of therelationship between two polypeptide sequences. In general, “similarity”means a comparison between the amino acids of two polypeptide chains, ona residue by residue basis, taking into account not only exactcorrespondences between a between pairs of residues, one from each ofthe sequences being compared (as for identity) but also, where there isnot an exact correspondence, whether, on an evolutionary basis, oneresidue is a likely substitute for the other. This likelihood has anassociated “score” from which the “% similarity” of the two sequencescan then be determined.

[0104] Methods for comparing the identity and similarity of two or moresequences are well known in the art. Thus for instance, programsavailable in the Wisconsin Sequence Analysis Package, version 9.1(Devereux J et al, Nucleic Acids Res, 12, 387-395, 1984, available fromGenetics Computer Group, Madison, Wis., USA), for example the programsBESTFIT and GAP, may be used to determine the % identity between twopolynucleotides and the % identity and the % similarity between twopolypeptide sequences. BESTFIT uses the “local homology” algorithm ofSmith and Waterman (J Mol Biol, 147,195-197, 1981, Advances in AppliedMathematics, 2, 482-489, 1981) and finds the best single region ofsimilarity between two sequences. BESTFIT is more suited to comparingtwo polynucleotide or two polypeptide sequences that are dissimilar inlength, the program assuming that the shorter sequence represents aportion of the longer. In comparison, GAP aligns two sequences, findinga “maximum similarity”, according to the algorithm of Neddleman andWunsch (J Mol Biol, 48, 443-453, 1970). GAP is more suited to comparingsequences that are approximately the same length and an alignment isexpected over the entire length. Preferably, the parameters “Gap Weight”and “Length Weight” used in each program are 50 and 3, forpolynucleotide sequences and 12 and 4 for polypeptide sequences,respectively. Preferably, % identities and similarities are determinedwhen the two sequences being compared are optimally aligned.

[0105] Other programs for determining identity and/or similarity betweensequences are also known in the art, for instance the BLAST family ofprograms (Altschul S F et al, J Mol Biol, 215, 403-410, 1990, Altschul SF et al, Nucleic Acids Res., 25:389-3402, 1997, available from theNational Center for Biotechnology Information (NCBI), Bethesda, Md., USAand accessible through the home page of the NCBI atwww.ncbi.nlm.nih.gov) and FASTA (Pearson W R, Methods in Enzymology,183, 63-99, 1990; Pearson W R and Lipman D J, Proc Nat Acad Sci USA, 85,2444-2448,1988, available as part of the Wisconsin Sequence AnalysisPackage).

[0106] Preferably, the BLOSUM62 amino acid substitution matrix (HenikoffS and Henikoff J G, Proc. Nat. Acad Sci. USA, 89, 10915-10919, 1992) isused in polypeptide sequence comparisons including where nucleotidesequences are first translated into amino acid sequences beforecomparison.

[0107] Preferably, the program BESTFIT is used to determine the %identity of a query polynucleotide or a polypeptide sequence withrespect to a reference polynucleotide or a polypeptide sequence, thequery and the reference sequence being optimally aligned and theparameters of the program set at the default value, as hereinbeforedescribed.

[0108] “Identity Index” is a measure of sequence relatedness which maybe used to compare a candidate sequence (polynucleotide or polypeptide)and a reference sequence. Thus, for instance, a candidate polynucleotidesequence having, for example, an Identity Index of 0.95 compared to areference polynucleotide sequence is identical to the reference sequenceexcept that the candidate polynucleotide sequence may include on averageup to five differences per each 100 nucleotides of the referencesequence. Such differences are selected from the group consisting of atleast one nucleotide deletion, substitution, including transition andtransversion, or insertion. These differences may occur at the 5′ or 3′terminal positions of the reference polynucleotide sequence or anywherebetween these terminal positions, interspersed either individually amongthe nucleotides in the reference sequence or in one or more contiguousgroups within the reference sequence. In other words, to obtain apolynucleotide sequence having an Identity Index of 0.95 compared to areference polynucleotide sequence, an average of up to 5 in every 100 ofthe nucleotides of the in the reference sequence may be deleted,substituted or inserted, or any combination thereof, as hereinbeforedescribed. The same applies mutatis mutatidis for other values of theIdentity Index, for instance 0.96, 0.97, 0.98 and 0.99.

[0109] Similarly, for a polypeptide, a candidate polypeptide sequencehaving, for example, an Identity Index of 0.95 compared to a referencepolypeptide sequence is identical to the reference sequence except thatthe polypeptide sequence may include an average of up to fivedifferences per each 100 amino acids of the reference sequence. Suchdifferences are selected from the group consisting of at least one aminoacid deletion, substitution, including conservative and non-conservativesubstitution, or insertion. These differences may occur at the amino- orcarboxy-terminal positions of the reference polypeptide sequence oranywhere between these terminal positions, interspersed eitherindividually among the amino acids in the reference sequence or in oneor more contiguous groups within the reference sequence. In other words,to obtain a polypeptide sequence having an Identity Index of 0.95compared to a reference polypeptide sequence, an average of up to 5 inevery 100 of the amino acids in the reference sequence may be deleted,substituted or inserted, or any combination thereof, as hereinbeforedescribed. The same applies mutatis mutatidis for other values of theIdentity Index, for instance 0.96, 0.97, 0.98 and 0.99.

[0110] The relationship between the number of nucleotide or amino aciddifferences and the Identity Index may be expressed in the followingequation:

n _(a) ≦x _(a)−(x _(a) •I),

[0111] in which:

[0112] n_(a) is the number of nucleotide or amino acid differences,

[0113] x_(a) is the total number of nucleotides or amino acids in asequence set forth in the Sequence Listing,

[0114] I is the Identity Index,

[0115] • is the symbol for the multiplication operator, and

[0116] in which any non-integer product of x_(a) and I is rounded downto the nearest integer prior to subtracting it from x_(a).

[0117] “Homolog” is a generic term used in the art to indicate apolynucleotide or polypeptide sequence possessing a high degree ofsequence relatedness to a reference sequence. Such relatedness may bequantified by determining the degree of identity and/or similaritybetween the two sequences as hereinbefore defined. Falling within thisgeneric term are the terms “ortholog”, and “paralog”. “Ortholog” refersto a polynucleotide or polypeptide that is the functional equivalent ofthe polynucleotide or polypeptide in another species. “Paralog” refersto a polynucleotide or polypeptide that within the same species which isfunctionally similar.

[0118] “Fusion protein” refers to a protein encoded by two, oftenunrelated, fused genes or fragments thereof. In one example, EP-A-0 464533-A discloses fusion proteins comprising various portions of constantregion of immunoglobulin molecules together with another human proteinor part thereof. In many cases, employing an immunoglobulin Fc region asa part of a fusion protein is advantageous for use in therapy anddiagnosis resulting in, for example, improved pharmacokinetic properties[see, e.g., EP-A 0232 262]. On the other hand, for some uses it would bedesirable to be able to delete the Fc part after the fusion protein hasbeen expressed, detected and purified.

[0119] All publications and references, including but not limited topatents and patent applications, cited in this specification are hereinincorporated by reference in their entirety as if each individualpublication or reference were specifically and individually indicated tobe incorporated by reference herein as being fully set forth. Any patentapplication to which this application claims priority is alsoincorporated by reference herein in its entirety in the manner describedabove for publications and references. TABLE I Corresponding GSK NucleicAcid Protein Gene Name Gene ID SEQ ID NO's SEQ ID NO's sbg237163LIPASE237163 SEQ ID NO: 1 SEQ ID NO: 23 sbg251170CEAa 251170 SEQ ID NO: 2 SEQID NO: 24 SEQ ID NO: 3 SEQ ID NO: 25 sbg389686WNT15a 389686 SEQ ID NO: 4SEQ ID NO: 26 SEQ ID NO: 5 SEQ ID NO: 27 sbg236015LIPASE 236015 SEQ IDNO: 6 SEQ ID NO: 28 SEQ ID NO: 7 SEQ ID NO: 29 sbg417005 417005 SEQ IDNO: 8 SEQ ID NO: 30 LAMININ_ALPHA SEQ ID NO: 9 SEQ ID NO: 31sbg425649KINASEa 425649 SEQ ID NO: 10 SEQ ID NO: 32 sbg419582 419582 SEQID NO: 11 SEQ ID NO: 33 PROTOCADHERIN SEQ ID NO: 12 SEQ ID NO: 34sbg453915 453915 SEQ ID NO: 13 SEQ ID NO: 35 TECTORINaSBh385630.antiinflam 385630 SEQ ID NO: 14 SEQ ID NO: 36 SEQ ID NO: 15SEQ ID NO: 37 sbg471005nAChR 471005 SEQ ID NO: 16 SEQ ID NO: 38sbg442445PROa 442445 SEQ ID NO: 17 SEQ ID NO: 39 sbg456548CytoRa 456548SEQ ID NO: 18 SEQ ID NO: 40 SEQ ID NO: 19 SEQ ID NO: 41 sbg456548CytoRa456548b SEQ ID NO: 20 SEQ ID NO: 42 sbg442358PROa 442358 SEQ ID NO: 21SEQ ID NO: 43 SEQ ID NO: 22 SEQ ID NO: 44

[0120] TABLE II Cell Localization Gene Closest Polynuclotide ClosestPolypeptide by (by Gene Name Family by homology homology homology)sbg237163 Pancreatic GB: AC011328 Mouse pancreatic lipase SecretedLIPASE lipase Direct submitted (OCT- related protein 1, gi: 06-1999)Genome 9256628 Therapeutics Remington, S. G., Corporation, 100 Lima, P.H. and Nelson, J. D. Beaver Street, Invest. Ophthalmol. Vis. Waltham, MA02453, Sci. 40 (6), 1081-1090 USA (1999) sbg251170CEAa Carcinoem GB:AC020914 Mouse putative protein, Secreted bryonic Submitted (JAN-12- gi:12842545 antigen 2000) Production Carninci, P., Shibata, Y., SequencingFacility, Hayatsu, N., Sugahara, Y., DOE Joint Shibata, K., Itoh, M.,Genome Institute, 2800 Konno, H., Okazaki, Y., Mitchell Drive, WalnutMuramatsu, M. and Creek, CA 94598, USA Hayashizaki, Y. Genome Res. 10(10), 1617-1630 (2000). sbg389686 WNT15 GB: AC015855 Chicken WNT14protein, Secreted WNT15a Directly submitted (NOV- gi: 3915306 17-1999)Whitehead Bergstein I, Eisenberg L M, Institute/MIT Center Bhalerao J,Jenkins N A, for Genome Research, Copeland N G, Osborne 320 CharlesStreet, M P, Bowcock A M, Brown Cambridge, MA 02141, A M; 1997; GenomicsUSA. 46: 450-8. sbg236015LIPASE Lysosomal GB: AL358532 Rat linguallipase, Secreted acid Directly submitted (DEC- gi: 126307 lipase15-2000) by Sanger Docherty, A. J., Centre, Hinxton, Bodmer, M. W.,Angal, S., Cambridgeshire, CB 10 Verger, R., Riviere, C., 1SA, UK. Lowe,P. A., Lyons, A., Emtage, J. S. and Harris, T. J. Nucleic Acids Res. 13(6), 1891-1903 (1985) sbg417005LAMININ_(—) Laminin GB: AL354836 Humanlaminin alpha 5, Secreted ALPHA alpha Direct submitted (MAY- gi:12274842 02-2000) Sanger Submitted (FEB-14-2001) Centre, Hinxton, bySanger Centre, Hinxton, Cambridgeshire, CB 10 Cambridgeshire, CB 10 1SA1SA, UK. sbg425649KINASEa Casein GB: AL356107 Human casein kinase I-Cytosolic kinase I- Submitted (MAY-16- alpha, alpha 2000) by gi: 2134872Sanger Centre, Fish, K. J., Hinxton, Cegielska, A., Cambridgeshire, CB10 Getman, M. E., 1SA, UK. Landes, G. M. and Virshup, D. M. J. Biol.Chem. 270 (25), 14875-14883 (1995) sbg419582PROTOCADHERIN ProtocadherinGB: AL355593 Human protocadherin 68 Secreted Direct submitted (MAY- gi:11433373 17-2000) Sanger Submitted (NOV-16-2000) Centre, Hinxton, byNational Center for Cambridgeshire, CB 10 Biotechnology 1SA, UK.Information, NIH, Bethesda, MD 20894, USA sbg453915TECTORINa TectorinSC: AL157786 Mouse tectorin beta, Secreted Beta Submitted (MAY-04- gi:7363457 2001) by Sanger Legan, P. K., Rau, A., Centre, Hinxton, Keen, J.N. and Cambridgeshire, CB 10 Richardson, G. P. 1SA, UK. J. Biol. Chem.272 (13), 8791-8801 (1997) SBh385630. Lipase GB: AC015525 Rabbitlacrimal lipase, Secreted antiinflam Submitted (NOV-16- gi: 135608841999) by Whitehead Submitted (FEB-20-2001) Institute/MIT CenterOphthalmology, Regions for Genome Research, Hospital, 640 Jackson 320Charles Street, Street, St. Paul, MN 55101, Cambridge, MA 02141, USA USAsbg471005nAChR Nicotinic GB: AC060812 Human cholinergic Membrane-acetylcholine Direct submitted receptor, nicotinic, alpha bound receptor(APR-20-2000) polypeptide 10, Whitehead gi: 11138123 Institute/MITLustig, L. R., Peng, H., Center for Hiel, H., Yamamoto, T. Genome andFuchs, P. A. Research, 320 Genomics 73 (3), 272- Charles Street, 283(2001) Cambridge, MA 02141, USA sbg442445PROa Leucine rich GB: AC060234RIKEN cDNA mouse Cytosolic repeat protein Submitted 4930442L21 gene(APR-20-2000) Carninci, P., Shibata, Y., Genome Hayatsu, N.,Therapeutics Sugahara, Y., Shibata, K., Corporation, 100 Itoh, M.,Konno, H., Beaver Street, Okazaki, Y., Waltham, Muramatsu, M. and MA02453, USA Hayashizaki, Y. Genome Res. 10 (10), 1617-1630 (2000)sbg456548CytoRa Cytokine GB: AL158138 Human IL20 receptor, Membrane-receptor Submitted (JAN- gi: 7657691 bound 20-2001) by Xie M H, AggarwalS, Sanger Centre, Ho W H, Foster J, Zhang Hinxton, Z, Stinson J, Wood WI, Cambridgeshire, Goddard AD and Gurney CB 10 1SA, UK. A L. J. Biol.Chem. 275 (40), 31335-31339 (2000) sbg442358PROa Leucine rich GB:AL139099 Human EXMAD-9 Membrane- repeat protein Submitted (MAY-geneseqp: AAB27231 bound 23-2000) by Submitted by INCYTE Genoscope-GENOMICS INC Centre National Application and de Sequencage: publicationdate: BP 191 91006 WO200068380-A2, NOV- EVRY cedex — 16-00 FRANCE

[0121] TABLE III Associated Gene Name Uses Diseases sbg237163 Anembodiment of the invention is the use of sbg237163 Cancer, infection,LIPASE LIPASE as replacement enzymes for patients with chronicautoimmune pancreatitis. A close homologue of sbg237163 LIPASE disorder,is pancreatic lipase. Pancreatic lipase hydrolyzes dietary hematopoieticlong chain triacylglycerol to free fatty acids and disorder, woundmonoacylglycerols in the intestinal lumen (Lowe M E, healing disorders,Rosenblum J L, and Strauss A W; 1989; J Biol Chem inflammation. 264:20042-8). Pancreatic steatorrhea and pancreatic diabetes are thedominant symptoms of patients in a certain stage of chronicpancreatitis. In this stage, the nutritional state is greatly disturbedand hypoglycemia and labile infection are involved. Pancreatic enzymereplacement therapy is the principal treatment method for pancreaticsteatorrhea (Nakamura T, Takeuchi T, and Tando Y; 1998; Pancreas 16:329-36. sbg251170CEAa An embodiment of the invention is the use ofCancer, sbg251170CEAa as cell-surface molecules mediating autoimmunecell-specific interactions in normal and neoplastic cells. A disorders,wound close homologue of sbg251170CEAa is healing disorders,carcinoembryonic antigen-related cell adhesion molecule hematopoietic 6.Carcinoembryonic antigen-related cell adhesion disorders and molecule 6is claimed to function as a cell-surface infection molecules mediatingcell-specific interactions in normal and neoplastic cells (1. Barnett T,Goebel S J, Nothdurft M A, Elting J J, Carcinoembryonic antigen family:characterization of cDNAs coding for NCA and CEA and suggestion ofnonrandom sequence variation in their conserved loop-domains. Genomics1988 Jul; 3(1): 59-66. 2. Inazawa J, Abe T, Inoue K, Misawa S, Oikawa S,Nakazato H, Yoshida M C. Regional assignment of nonspecificcross-reacting antigen (NCA) of the CEA gene family to chromosome 19 atband q13.2. Cytogenet Cell Genet 1989; 52(1-2): 28-31). sbg389686 Anembodiment of the invention is the use of Cancer, infection, WNT15asbg389686WNT15a in regulation of cell growth and autoimmunedifferentiation. Close homologues of disorder, sbg389686WNT15a are Wntproteins. Wnt proteins are hematopoietic involved in criticaldevelopmental processes in both disorder, wound vertebrates andinvertebrates and are implicated in healing disorders, regulation ofcell growth and differentiation in certain and inflammation adultmammalian tissues (Bergstein I, Eisenberg L M, Bhalerao J, Jenkins N A,Copeland N G, Osborne M P, Bowcock A M, Brown A M; 1997; Genomics 46:450-8). The Wnt gene family consists of at least 15 structurally relatedgenes that encode secreted extracellular signaling factors. Wntsignaling is involved in many mammalian developmental processes,including cell proliferation, differentiation and epithelial-mesenchymalinteractions, through which they contribute to the development oftissues and organs such as the limbs, the brain, the reproductive tractand the kidney. Evidence from tumor expression studies and transgenicanimals experiments suggests that inappropriate activation of the Wntsignaling pathway is a major feature in human neoplasia and thatoncogenic activation of this pathway can occur at many levels.Inappropriate expression of the Wnt ligand and Wnt binding proteins havebeen found in a variety of human tumors (Smalley M J, Dale T C; 1999;Cancer Metastasis Rev 18: 215-30). sbg236015LIPASE An embodiment of theinvention is the use of Cancer, infection, sbg236015LIPASE for treatinglipase deficiency. A autoimmune close homologue of sbg236015LIPASE islysosomal disorder, acid lipase. The lysosomal acid lipase catalyzes thehematopoietic deacylation of triacylglyceryl and cholesteryl ester coredisorder, wound lipids of endocytosed low density lipoproteins. Thishealing disorders, activity is deficient in patients with Wolman diseaseand inflammation, cholesteryl ester storage disease, which are caused bya Wolman disease, deficiency of lysosomal acid lipase activity,resulting in and cholesteryl massive accumulation of cholesteryl esterand ester storage triglycerides (Anderson R A, Sando G N; 1991; J Bioldisease Chem 266: 22479-84). sbg417005LAMININ_(—) An embodiment of theinvention is the use of Cancer, infection, ALPHA sbg417005LAMININ_ALPHAto promote myogenesis autoimmune in skeletal muscle, outgrowth ofneurites from central disorder, and peripheral neurons, and mesenchymalto epithelial hematopoietic transitions in kidney. A close homologue ofdisorder, wound sbg417005LAMININ_ALPHA is laminin. Laminins healingdisorders, trimers, composed of alpha, beta, and gamma chains, areinflammation, components of all basal laminae (BLs) throughout thecongenital bodies. In mammals they play at least three essentialmuscular roles. First, they are major structural elements of BLs,dystrophy, and forming one of two self-assembling networks to whichjunctional other glycoproteins and proteoglycans of the BL attach.epidermolysis Second, they interact with cell surface components suchbullosa as dystroglycan to attach cells to the extracellular matrix.Third, they are signaling molecules that interact with cellularreceptors such as the integrins to convey important information to thecell interior. The alpha chains are ligands for most cellular lamininreceptors. (Miner J H, Patton B L, Lentz S I, Gilbert D J, Snider W D,Jenkins N A, Copeland N G, Sanes J R; 1997; J Cell Biol 137: 685-701).sbg425649KINASEa An embodiment of the invention is the use of Cancer,wound sbg425649KINASEa in DNA replication and repair, healing disorders,membrane trafficking, neuroprotective, cytostatic, autoimmunecardioactive, immunomodulatory, muscular, vulnerary, disorders,gastrointestinal, nephrotropic, anti-infective, hematopoieticgynaecological and antibacterial activities, and can be disorders andused in gene therapy. Close homologues of infection sbg425649KINASEa ismammalian casein kinases I (CKI) and human prostate cancer associatedprotein. CKI belongs to a family of serine/threonine protein kinasesinvolved in diverse cellular processes including DNA replication andrepair, membrane trafficking, circadian rhythms and Wnt signaling. Humanprostate cancer associated proteins have neuroprotective, cytostatic,cardioactive, immunomodulatory, muscular, vulnerary, gastrointestinal,nephrotropic, anti-infective, gynaecological and antibacterialactivities, and can be used in gene therapy. sbg419582PROTOCADHERIN Anembodiment of the invention is the use of Cancer, infection,sbg419582PROTOCADHERIN in functional systems of autoimmune the nervoussystem, and may be involved in the disorder, formation of the neuralnetwork. A close homologue of hematopoietic sbg419582PROTOCADHERIN isprotocadherin. The disorder, wound expression of protocadherin isdevelopmentally healing disorders, regulated in a subset of thefunctional systems of the inflammation, nervous system, and may beinvolved in the formation Parkinson's of the neural network bysegregation of the brain nuclei disease, and mediation of the axonalconnections (Hirano S, Yan Huntington's Q, Suzuki S T; 1999; J Neurosci19: 995-1005). The chorea, and members of the cadherin superfamily aredivided into multiple sclerosis two groups: classical cadherin type andprotocadherin type. The current cadherins appear to have evolved fromprotocadherin (Suzuki S T; 1996; J Cell Sci 109: 2609-11).sbg453915TECTORINa An embodiment of the invention is the use ofInfection, cancer, sbg453915TECTORINa, a secreted protein, in cellularwound healing adhesion. A close homologue of disorders,sbg453915TECTORINa is mouse tectorin beta. The hemotopoieticbeta-tectorin is a protein of 36,074 Da that contains 4 disorders andconsensus N glycosylation sites and a single zona autoimmune pellucidadomain. It is similar to components of the disorders. sperm-egg adhesionsystem, and, as such may have a similar functional role (Legan P K, RauA, Keen J N, Richardson G P, The mouse tectorins. Modular matrixproteins of the inner ear homologous to components of the sperm-eggadhesion system. J Biol Chem 1997 Mar 28; 272(13): 8791-801). SBh385630.An embodiment of the invention is the use of Lematopoietic antiinflamSBh385630.antiinflam in gene therapy and are also disorders, woundsuggested to have cytokine and cell healing disorders,proliferation/differentiation activity, immune viral and bacterialstimulating (e.g. vaccines) or suppressing activity, infections, cancer,haematopoiesis regulating activity, tissue growth and autoimmuneactivity, activin/inhibinactivity, diseases chemotactic/chemokineticactivity, haemostatic and thrombolytic activity, receptor/ligandactivity, anti- inflammatory activity, cadherin/tumour invasionsuppressor activity, and tumour inhibition activity. Lipases are alsoreported to be useful for gene therapy (WO9957132-A1; Agostino, M. J.,filed by GENETICS INST INC.). Close homologues of SBh385630.antiinflaminclude lipases. sbg471005n An embodiment of the invention is the use ofCancer, infection, AChR sbg471005nAChR in physiological and behaviouralautoimmune processes of the brain. A close homologue of disorder,sbg471005nAChR is neuronal nicotinic acetylcholine hematopoieticreceptors. Neuronal nicotinic acetylcholine receptors disorder, woundare a family of ion channels which are widely healing disorders,distributed in the human brain. There are many inflammation, subtypes,and each has individual pharmacological and Alzheimer's functionalprofiles. They mediate the effects of nicotine, disease, and areinvolved in a number of physiological and Parkinson's behaviouralprocesses. Additionally they may be disease, and implicated in a numberof pathological conditions such schizophrenia as Alzheimer's disease,Parkinson's disease and schizophrenia (Paterson D, Nordberg A; 2000;Prog Neurobiol 61: 75-111). sbg442445PROa An embodiment of the inventionis the use of Inflammation, sbg442445PROa which may be involved inprotein- autoimmune protein interation and signal transduction in immunedisorders, asthma, system. sbg442445PROa was expressed predominantlyallergies in lung and spleen/lymph. It encodes a protein with andleucine rich repeats which may be involved in protein- sbg442445PROa-protein interation and signal transduction in immune associated systems.disorders sbg456548CytoRa The present gene has been cloned. Sybrman dataChronic and acute showed its high expression levels in placenta andinflammation, moderate levels in spleen and lymph. A close allergy,arthritis homologue of sbg456548CytoRa is another Class II (includingcytokine receptor, ZCYTOR7. An embodiment of the rheumatoid invention isthe use of sbg456548CytoRa, a decoy arthritis), receptor, in theidentification of other ligands, the septicemia, promotion ofanti-microbial activation of these cells, autoimmune and/or potentiatethe effectiveness of the natural ligand. diseases (e.g., Growth factorsare known to promote the progression of inflammatory cancer. A decoyreceptor could interfere with that bowel disease, process.Proliferation, survival and differentiation can psoriasis), betransduced from activated cytokine receptors (Cell transplant Signal.1998. 10(9): 619-628). Blocking these events rejection, graft vs. couldbe crucial in modulating various diseases. host disease, The decoyreceptor could potentially interfere with infection, stroke, binding ofthese or other putative ligands, preventing ischemia, acute downstreameffects (Blood. 1999. 94(6): 1943-1951). respiratory disease GM-CSF alsohas anti-apoptotic activity. A decoy syndrome, asthma, receptor mightthen be able to block GM-CSF's anti- restenosis, brain apoptotic actionswhen appropriate (Mol Biol Cell. injury, AIDS, bone 1999. 10(11):3959-3970). Roles for blocking the diseases, cancer, activity of thedecoy receptor can be envisioned. GM- atheroschlerosis, CSF promotesanti-microbial functions of mature Alzheimers neutrophils. Inhibitingthe activity of an interfering disease,, decoy receptor could promoteanti-microbial activation hematopoietic of these cells. Furthermore,rhGM-CSF is in wide disorder, and clinical use to fight acute myeloidleukemia wound healing (Haematologica. 1991. 82(2): 239-245). Inhibitionof a disorder decoy receptor could potentiate the effectiveness of thenatural ligand. sbg442358PROa An embodiment of the invention is the useof Cancer, sbg442358PROa useful in the prevention and treatmentautoimmune of cancers, cell proliferation, cardiovascular, disorders,reproductive, immune, musculoskeletal, developmental hemotopoietic andgastrointestinal disorders and inflammation. Close disorders, woundhomologues of sbg442358PROa are human protein healing disorders B27231and Drosophila LRR47 that also contains and infections leucine-richrepeats (LRRs) motifs. LRR has been found in a variety of extracellular,membrane and cytoplasmic proteins and are believed to mediate specificprotein-protein interactions and to function in cellular adhesion(Ntwasa, M., Buchanan, S. G. and Gay, N. J. Biochim. Biophys. Acta 1218(2), 181-186 (1994)).

[0122] TABLE IV Quantitative, Tissue-specific, mRNA expression detectedusing SybrMan Quantitative, tissue-specific, mRNA expression patterns ofthe genes were measured using SYBR- Green Quantitative PCR (AppliedBiosystems, Foster City, CA; see Schmittgen T. D. et al., AnalyticalBiochemistry 285: 194-204, 2000) and human cDNAs prepared from varioushuman tissues. Gene-specific PCR primers were designed using the firstnucleic acid sequence listed in the Sequence List for each gene. Resultsare presented as the number of copies of each specific gene's mRNAdetected in 1 ng mRNA pool from each tissue. Two replicate mRNAmeasurements were made from each tissue RNA. Tissue-Specific mRNAExpression (copies per ng mRNA; avg. ± range for 2 data points pertissue) Gene Skeletal Name Brain Heart Lung Liver Kidney muscleIntestine Spleen/lymph Placenta Testis Gene Name sbg237163LIPASEsbg237163LIPASE 5 ± 0 8 ± 2 7 ± 2 −6 ± 1 5 ± 1 5 ± 2 4 ± 6 3 ± 2 1 ± 147 ± 1  Gene Name sbg251170CEAa sbg251170CEAa 3 ± 1 19 ± 30 ± −5 ± 3 3 ±1 5 ± 5 21 ± 2 33 ± 4  22 ± 3  14 ± 0   1  5 In each gene's first subsettable, two replicate measurements of gene of identification (GOI) mRNAwere measured from various human tissues (column 2 and 3). The averageGOI mRNA copies of the two replicates were made from each tissue RNA(column 4). The average amount of 18S rRNA from each tissue RNA wasmeasured (column 5) and used for normalization. To make each tissue withthe same amount of 50 ng of 18S rRNA, the normalization factor (column6) was calculated by dividing 50 ng with the amount of 18S rRNA measuredfrom each tissue (column 5). The mRNA copies per 50 ng of total RNA wereobtained by multipling each GOI normalization factor and average mRNAcopies (column7). Fold changes shown in each gene's second subset tablewere only calculated for disease tissues which have a normalcounterpart. There are blanks in the fold change column for all samplesthat do not have counterparts. In addition, the fold change calculationsare the fold change in the disease sample as compared to the normalsample. Accordingly, there will not be a fold change calculation next toany of the normal samples. For patient matched cancer pairs (colon,lung, and breast), each tumor is compared to its specific normalcounterpart. When patient-matched normal/disease pairs do not exist,each disease sample was compared back to the average of all the normalsamples of that same tissue type. For example, normal brain from thesame patient that provided Alzheimer's brain is not applicable. Threenormal brain samples and 4 Alzheimer's brain samples are used in thefold change. Three normal samples were averaged, and each of theAlzheimer's samples was compared back to that average. Abbreviations ALZAlzheimer's Disease CT CLONTECH (1020 East Meadow Circle Palo Alto, CA94303-4230, USA) KC Sample prepared by GSK investigator COPD chronicobstructive pulmonary disease endo endothelial VEGF vascular endothelialgrowth factor bFGF basic fibroblast growth factor BM bone marrow osteoosteoblast OA osteoarthritis RA rheumatoid arthritis PBL peripheralblood lymphocytes PBMNC peripheral blood mononuclear cells HIV humanimmunodeficiency virus HSV Herpes simplex virus HPV human papillomavirus Gene Name sbg389686WNT15a Strong expression in Brain and dendriticcells. Brain expression may be from presence of glial cells. Expressionin RA and OA synovium along with dendritic cells suggests a role forthis protein in these diseases. Down regulation in ischemic and dilatedheart indicates that replacement of protein could be therapeutic.

[0123] copies of mRNA detected/ Mean GOI Mean GOI Average 18S 50 ng/18S50 ng Sample copies copies GOI rRNA rRNA total sbg389686WNT15a(sample 1) (sample 2) Copies (ng) (ng) RNA Subcutaneous 0.00 0.00 0.003.06 16.34 0.00 Adipocytes Zenbio Subcutaneous Adipose 0.00 1.71 0.860.96 52.36 44.76 Zenbio Adrenal Gland Clontech 2.29 4.18 3.24 0.61 81.97265.16 Whole Brain Clontech 698.52 625.01 661.77 7.24 6.91 4570.20 FetalBrain Clontech 4.14 6.78 5.46 0.48 103.95 567.57 Cerebellum Clontech2.02 3.63 2.83 2.17 23.04 65.09 Cervix 3.16 10.14 6.65 2.42 20.66 137.40Colon 2.48 3.44 2.96 2.71 18.45 54.61 Endometrium 2.69 5.20 3.95 0.7368.21 269.10 Esophagus 10.67 3.24 6.96 1.37 36.50 253.83 Heart Clontech9.26 6.07 7.67 1.32 37.88 290.34 Hypothalamus 7.10 5.16 6.13 0.32 155.28951.86 Ileum 2.04 10.37 6.21 2.58 19.38 120.25 Jejunum 36.78 27.16 31.976.60 7.58 242.20 Kidney 16.46 16.55 16.51 2.12 23.58 389.27 Liver 14.073.34 8.71 1.50 33.33 290.17 Fetal Liver Clontech 4.60 8.89 6.75 10.404.81 32.43 Lung 3.11 10.49 6.80 2.57 19.46 132.30 Mammary Gland 3.2810.61 6.95 13.00 3.85 26.71 Clontech Myometrium 1.79 13.84 7.82 2.3421.37 166.99 Omentum 1.96 2.65 2.31 3.94 12.69 29.25 Ovary 4.50 1.713.11 4.34 11.52 35.77 Pancreas 3.40 2.41 2.91 0.81 61.80 179.54 Head ofPancreas 2.22 4.63 3.43 1.57 31.85 109.08 Parotid Gland 5.48 2.07 3.785.48 9.12 34.44 Placenta Clontech 15.15 12.80 13.98 5.26 9.51 132.84Prostate 3.39 7.44 5.42 3.00 16.67 90.25 Rectum 2.98 3.94 3.46 1.2340.65 140.65 Salivary Gland 3.24 1.61 2.43 7.31 6.84 16.59 ClontechSkeletal Muscle 2.01 1.55 1.78 1.26 39.68 70.63 Clontech Skin 2.69 3.453.07 1.21 41.32 126.86 Small Intestine 5.39 1.67 3.53 0.98 51.07 180.29Clontech Spleen 3.96 2.52 3.24 4.92 10.16 32.93 Stomach 1.08 5.33 3.212.73 18.32 58.70 Testis Clontech 3.27 2.88 3.08 0.57 87.87 270.21 ThymusClontech 5.43 4.42 4.93 9.89 5.06 24.90 Thyroid 2.32 3.01 2.67 2.7718.05 48.10 Trachea Clontech 1.64 4.25 2.95 9.71 5.15 15.16 UrinaryBladder 3.63 6.81 5.22 5.47 9.14 47.71 Uterus 31.55 11.10 21.33 5.349.36 199.67 copies of Reg mRNA number Mean detected/50 ng Fold Change inSample (GSK GOI total Disease sbg389686WNT15a identifier) copies RNASample Population colon normal GW98-167 21941 36.16 72.32 colon normalcolon tumor GW98-166 21940 71.5 143.00 colon tumor 1.977323009 colonnormal GW98-178 22080 2.09 4.18 colon normal colon tumor GW98- 177 220609.84 19.68 colon tumor 4.708133971 colon normal GW98-561 23514 13.0926.18 colon normal colon tumor GW98-560 23513 15.11 30.22 colon tumor1.154316272 colon normal GW98-894 24691 8.62 17.24 colon normal colontumor GW98-893 24690 5.76 11.52 colon tumor −1.496527778 lung normalGW98-3 20742 140.19 280.38 lung normal lung tumor GW98-2 20741 1.67 3.34lung tumor −83.94610778 lung normal GW97-179 20677 60.54 121.08 lungnormal lung tumor GW97- 178 20676 135.62 271.24 lung tumor 2.240171787lung normal GW98-165 21922 257.96 515.92 lung normal lung tumor GW98-16421921 61.69 123.38 lung tumor −4.181552926 lung normal GW98-282 2258449.3 98.60 lung normal lung tumor GW98-281 22583 12.39 24.78 lung tumor−3.979015335 breast normal GW00-392 28750 71.94 71.94 breast normalbreast tumor GW00-391 28746 41.4 82.80 breast tumor 1.150959133 breastnormal GW00-413 28798 19.37 19.37 breast normal breast tumor GW00-41228797 1.13 2.26 breast tumor −8.57079646 breast normal GW00- 27592-958.19 8.19 breast 235:238 normal breast tumor GW00- 27588-91 38.27 38.27breast tumor 4.672771673 231:234 breast normal GW98-621 23656 77.26154.52 breast normal breast tumor GW98-620 23655 37.57 75.14 breasttumor −2.056428001 brain normal BB99-542 25507 597.17 1194.34 brainnormal brain normal BB99-406 25509 104.34 208.68 brain normal brainnormal BB99-904 25546 282.15 564.30 brain normal brain stage 5 ALZ BB99-25502 84.26 168.52 brain stage 5 −3.891367988 874 ALZ brain stage 5 ALZBB99- 25503 247.01 494.02 brain stage 5 −1.327422641 887 ALZ brain stage5 ALZ BB99- 25504 173.02 346.04 brain stage 5 −1.895079567 862 ALZ brainstage 5 ALZ BB99- 25542 253.73 507.46 brain stage 5 −1.292266057 927 ALZCT lung KC normal 146.22 292.44 CT lung lung 26 KC normal 150.46 150.46lung 26 lung 27 KC normal 0 0.00 lung 27 lung 24 KC COPD 4.76 4.76 lung24 −23.36292017 lung 28 KC COPD 10.06 10.06 lung 28 −11.05442346 lung 23KC COPD 2.75 2.75 lung 23 −40.43909091 lung 25 KC COPD 1.93 1.93 lung 25asthmatic lung 29321 20.88 20.88 asthmatic −5.326029693 ODO3112 lungasthmatic lung 29323 133.29 266.58 asthmatic 2.397140481 ODO3433 lungasthmatic lung 29322 322.77 645.54 asthmatic 5.804824315 ODO3397 lungasthmatic lung 29325 43.52 87.04 asthmatic −1.277659697 ODO4928 lungendo cells KC control 1.89 1.89 endo cells endo VEGF KC 0 0.00 endo VEGF−1.89 endo bFGF KC 1.17 1.17 endo bFGF −1.615384615 heart Clontechnormal 153.9 307.80 heart heart (T-1) ischemic 29417 137.74 275.48 heartT-1 −1.117322492 heart (T-14) non- 29422 87.79 175.58 heart T-14−1.753047044 obstructive DCM heart (T-3399) DCM 29426 43.68 87.36 heartT-3399 −3.523351648 adenoid GW99-269 26162 17.62 35.24 adenoid tonsilGW98-280 22582 52.34 104.68 tonsil T cells PC00314 28453 8.45 16.90 Tcells PBMNC KC 1.99 1.99 PBMNC monocyte KC 4.74 9.48 monocyte B cellsPC00665 28455 7.65 15.30 B cells dendritic cells 28441 194.97 389.94dendritic cells neutrophils 28440 2.13 2.13 neutrophils eosinophils28446 7.25 14.50 eosinophils BM unstim KC 0 0.00 BM unstim BM stim KC 00.00 BM stim 0 osteo dif KC 1.48 1.48 osteo dif osteo undif KC 7.41 7.41osteo undif 5.006756757 chondrocytes 26.64 66.60 chondrocytes OASynovium IP12/01 29462 476.3 476.30 OA Synovium OA Synovium NP10/0129461 151.36 302.72 OA Synovium OA Synovium NP57/00 28464 165.01 330.02OA Synovium RA Synovium NP03/01 28466 84.02 168.04 RA Synovium RASynovium NP71/00 28467 184.75 369.50 RA Synovium RA Synovium NP45/0028475 223.3 446.60 RA Synovium OA bone (biobank) 29217 72.31 72.31 OAbone (biobank) OA bone Sample 1 J. Emory 10.46 20.92 OA bone OA boneSample 2 J. Emory 111.79 223.58 OA bone Cartilage (pool) Normal 215.54431.08 Cartilage (pool) Cartilage (pool) OA 81.85 163.70 Cartilage−2.633353696 (pool) PBL unifected 28441 2.31 4.62 PBL unifected PBL HIVIIIB 28442 2.28 4.56 PBL HIV −1.013157895 IIIB MRC5 uninfected 291582.37 4.74 MRC5 (100%) uninfected (100%) MRC5 HSV strain F 29178 37.575.00 MRC5 HSV 15.82278481 strain F W12 cells 29179 0.93 1.86 W12 cellsKeratinocytes 29180 1.33 2.66 Keratinocytes

[0124] Gene Name sbg389686WNT15a Fold Change in Disease PopulationRelative to Disease tissues Normal colon tumor 1.98 colon tumor 4.71colon tumor 1.15 colon tumor −1.50 lung tumor −83.95 lung tumor 2.24lung tumor −4.18 lung tumor −3.98 breast tumor 1.15 breast tumor −8.57breast tumor 4.67 breast tumor −2.06 brain stage 5 ALZ −3.89 brain stage5 ALZ −1.33 brain stage 5 ALZ −1.90 brain stage 5 ALZ −1.29 lung 24−23.36 lung 28 −11.05 lung 23 −40.44 asthmatic lung −5.33 asthmatic lung2.40 asthmatic lung 5.80 asthmatic lung −1.28 endo VEGF −1.89 endo bFGF−1.62 heart T-1 −1.12 heart T-14 −1.75 heart T-3399 −3.52 BM stim 0.00osteo undif 5.01 Cartilage (pool) −2.63 PBL HIV IIIB −1.01 MRC5 HSVstrain F 15.82

[0125] Gene Name sbg236015LIPASE

[0126] Strongly expressed in neutrophils and eosinophils suggesting animmune system function. Additional expression is seen in RA and OAsynovium and 1/3 OA bone samples. This suggests an involvement of 236015in RA and OA. The high expression in skin when taken together withexpression in neutrophils and eosinophils suggests possible involvementin immune pathologies of the skin ie. Eosinophilia, psoriasis andeczema. The expression in eosinophils also suggests involvement inallergic reactions. Expression in neutrophils suggests role inanti-infectives. copies of mRNA 50 ng/ detected/ Mean GOI Mean GOIAverage 18S 18S 50 ng Sample copies copies GOI rRNA rRNA totalsbg236015LIPASE (sample 1) (sample 2) Copies (ng) (ng) RNA Subcutaneous0.00 11.45 5.73 3.06 16.34 93.55 Adipocytes Zenbio Subcutaneous Adipose0.00 1.33 0.67 0.96 52.36 34.82 Zenbio Adrenal Gland Clontech 0.52 5.042.78 0.61 81.97 227.87 Whole Brain Clontech 15.73 14.55 15.14 7.24 6.91104.56 Fetal Brain Clontech 1.02 0.94 0.98 0.48 103.95 101.87 CerebellumClontech 0.38 0.39 0.39 2.17 23.04 8.87 Cervix 16.33 20.03 18.18 2.4220.66 375.62 Colon 32.41 50.89 41.65 2.71 18.45 768.45 Endometrium 0.400.42 0.41 0.73 68.21 27.97 Esophagus 5.45 22.47 13.96 1.37 36.50 509.49Heart Clontech 0.92 0.00 0.46 1.32 37.88 17.42 Hypothalamus 0.50 1.591.05 0.32 155.28 162.27 Ileum 41.95 1.51 21.73 2.58 19.38 421.12 Jejunum7.59 15.40 11.50 6.60 7.58 87.08 Kidney 5.32 6.82 6.07 2.12 23.58 143.16Liver 12.64 19.46 16.05 1.50 33.33 535.00 Fetal Liver Clontech 10.025.90 7.96 10.40 4.81 38.27 Lung 22.86 24.78 23.82 2.57 19.46 463.42Mammary Gland 1.53 20.56 11.05 13.00 3.85 42.48 Clontech Myometrium16.05 1.34 8.70 2.34 21.37 185.79 Omentum 8.33 9.88 9.11 3.94 12.69115.55 Ovary 8.22 14.40 11.31 4.34 11.52 130.30 Pancreas 0.00 1.58 0.790.81 61.80 48.83 Head of Pancreas 0.00 1.98 0.99 1.57 31.85 31.53Parotid Gland 5.30 11.45 8.38 5.48 9.12 76.41 Placenta Clontech 11.931.22 6.58 5.26 9.51 62.50 Prostate 0.00 0.00 0.00 3.00 16.67 0.00 Rectum6.96 1.27 4.12 1.23 40.65 167.28 Salivary Gland 0.34 0.53 0.44 7.31 6.842.98 Clontech Skeletal Muscle 176.88 0.41 88.65 1.26 39.68 3517.66Clontech Skin 95.17 147.16 121.17 1.21 41.32 5006.82 Small Intestine0.35 1.31 0.83 0.98 51.07 42.39 Clontech Spleen 105.73 80.76 93.25 4.9210.16 947.61 Stomach 0.56 3.73 2.15 2.73 18.32 39.29 Testis Clontech0.79 0.78 0.79 0.57 87.87 68.98 Thymus Clontech 22.00 22.48 22.24 9.895.06 112.44 Thyroid 0.65 0.48 0.57 2.77 18.05 10.20 Trachea Clontech1.20 0.00 0.60 9.71 5.15 3.09 Urinary Bladder 5.59 8.67 7.13 5.47 9.1465.17 Uterus 19.26 27.10 23.18 5.34 9.36 217.04 copies of Reg mRNAnumber Mean detected/50 ng Fold Change in Sample (GSK GOI total Diseasesbg236015LIPASE identifier) copies RNA Sample Population colon normalGW98-167 21941 58.7 117.40 colon normal colon tumor GW98-166 21940300.92 601.84 colon tumor 5.126405451 colon normal GW98-178 22080 8.7817.56 colon normal colon tumor GW98-177 22060 23.74 47.48 colon tumor2.703872437 colon normal GW98-561 23514 27.1 54.20 colon normal colontumor GW98-560 23513 39.16 78.32 colon tumor 1.44501845 colon normalGW98-894 24691 10.15 20.30 colon normal colon tumor GW98-893 24690144.58 289.16 colon tumor 14.24433498 lung normal GW98-3 20742 165.8331.60 lung normal lung tumor GW98-2 20741 80.9 161.80 lung tumor−2.049443758 lung normal GW97-179 20677 37.81 75.62 lung normal lungtumor GW97-178 20676 109.72 219.44 lung tumor 2.90187781 lung normalGW98-165 21922 150.06 300.12 lung normal lung tumor GW98-164 21921169.73 339.46 lung tumor 1.131080901 lung normal GW98-282 22584 489.42978.84 lung normal lung tumor GW98-281 22583 188.22 376.44 lung tumor−2.600255021 breast normal GW00-392 28750 44.86 44.86 breast normalbreast tumor GW00-391 28746 46.35 92.70 breast tumor 2.06642889 breastnormal GW00-413 28798 16.35 16.35 breast normal breast tumor GW00-41228797 55.98 111.96 breast tumor 6.847706422 breast normal GW00- 27592-953.84 3.84 breast 235:238 normal breast tumor GW00- 27588-91 35.8 35.80breast tumor 9.322916667 231:234 breast normal GW98-621 23656 12.1424.28 breast normal breast tumor GW98-620 23655 44.85 89.70 breast tumor3.694398682 brain normal BB99-542 25507 26.03 52.06 brain normal brainnormal BB99-406 25509 14.78 29.56 brain normal brain normal BB99-90425546 3.39 6.78 brain normal brain stage 5 ALZ BB99- 25502 35.71 71.42brain stage 5 2.423755656 874 ALZ brain stage 5 ALZ BB99- 25503 9.1118.22 brain stage 5 −1.617270399 887 ALZ brain stage 5 ALZ BB99- 255048.18 16.36 brain stage 5 −1.801140994 862 ALZ brain stage 5 ALZ BB99-25542 46.37 92.74 brain stage 5 3.147285068 927 ALZ CT lung KC normal80.77 161.54 CT lung lung 26 KC normal 233.65 233.65 lung 26 lung 27 KCnormal 75.27 75.27 lung 27 lung 24 KC COPD 68.64 68.64 lung 24−1.876821096 lung 28 KC COPD 94.1 94.10 lung 28 −1.369022317 lung 23 KCCOPD 88.48 88.48 lung 23 −1.455978752 lung 25 KC normal 44.84 44.84 lung25 asthmatic lung ODO3112 29321 111.42 111.42 asthmatic −1.156210734lung asthmatic lung ODO3433 29323 566.5 1133.00 asthmatic 8.794876771lung asthmatic lung ODO3397 29322 262.77 525.54 asthmatic 4.079487677lung asthmatic lung ODO4928 29325 367.52 735.04 asthmatic 5.70572482lung endo cells KC control 3.23 3.23 endo cells endo VEGF KC 3.41 3.41endo VEGF 1.055727554 endo bFGF KC 0 0.00 endo bFGF −3.23 heart Clontechnormal 0 0.00 heart heart (T-1) ischemic 29417 35.96 71.92 heart T-171.92 heart (T-14) non- 29422 18.72 37.44 heart T-14 37.44 obstructiveDCM heart (T-3399) DCM 29426 37.97 75.94 heart T-3399 75.94 adenoidGW99-269 26162 14.17 28.34 adenoid tonsil GW98-280 22582 51.21 102.42tonsil T cells PC00314 28453 111.1 222.20 T cells PBMNC KC 162.01 162.01PBMNC monocyte KC 90.49 180.98 monocyte B cells PC00665 28455 109.71219.42 B cells dendritic cells 28441 2.44 4.88 dendritic cellsneutrophils 28440 1110.91 1110.91 neutrophils eosinophils 28446 835.721671.44 eosinophils BM unstim KC 181.05 181.05 BM unstim BM stim KC93.96 93.96 BM stim −1.92688378 osteo dif KC 0 0.00 osteo dif osteoundif KC 0.72 0.72 osteo undif 0.72 chondrocytes 2.03 5.08 chondrocytesOA Synovium IP12/01 29462 27.82 27.82 OA Synovium OA Synovium NP10/0129461 84.94 169.88 OA Synovium OA Synovium NP57/00 28464 46.58 93.16 OASynovium RA Synovium NP03/01 28466 248.24 496.48 RA Synovium RA SynoviumNP71/00 28467 148.32 296.64 RA Synovium RA Synovium NP45/00 28475 260.28520.56 RA Synovium OA bone (biobank) 29217 10.27 10.27 OA bone (biobank)OA bone Sample 1 J. Emory 17.32 34.64 OA bone OA bone Sample 2 J. Emory657.01 1314.02 OA bone Cartilage (pool) Normal 59.17 118.34 Cartilage(pool) Cartilage (pool) OA 23.33 46.66 Cartilage −2.53621946 (pool) PBLunifected 28441 23.51 47.02 PBL unifected PBL HIV IIIB 28442 5.86 11.72PBL HIV −4.011945392 IIIB MRC5 uninfected 29158 3.79 7.58 MRC5 (100%)uninfected (100%) MRC5 HSV strain F 29178 80.19 160.38 MRC5 HSV21.15831135 strain F W12 cells 29179 95.42 190.84 W12 cellsKeratinocytes 29180 16.18 32.36 Keratinocytes

[0127] Gene Name sbg236015LIPASE Fold Change in Disease PopulationRelative to Disease tissues Normal colon tumor 5.13 colon tumor 2.70colon tumor 1.45 colon tumor 14.24 lung tumor −2.05 lung tumor 2.90 lungtumor 1.13 lung tumor −2.60 breast tumor 2.07 breast tumor 6.85 breasttumor 9.32 breast tumor 3.69 brain stage 5 ALZ 2.42 brain stage 5 ALZ−1.62 brain stage 5 ALZ −1.80 brain stage 5 ALZ 3.15 lung 24 −1.88 lung28 −1.37 lung 23 −1.46 asthmatic lung −1.16 asthmatic lung 8.79asthmatic lung 4.08 asthmatic lung 5.71 endo VEGF 1.06 endo bFGF −3.23heart T-1 71.92 heart T-14 37.44 heart T-3399 75.94 BM stim −1.93 osteoundif 0.72 Cartilage (pool) −2.54 PBL HIV IIIB −4.01 MRC5 HSV strain F21.16

[0128] Gene Name sbg417005LAMININ

[0129] Expression in adenoid, tonsil and B-cells with corroboratingexpression in RA/OA samples and asthmatic lung (1/4) suggestsinvolvement in these diseases. Strong expression in brain withoverexpression in Alzheimer's disease indicates a role in AD. Downregulation in HSV infected cells suggests potential host cell factor.Expression in colon and lung normal/tumor pairs without corroboratingexpression in normal tissues suggests immune cell infiltrates. copies ofmRNA detected/ Mean GOI Mean GOI Average 18S 50 ng/18S 50 ng Samplecopies copies GOI rRNA rRNA total sbg417005LAMININ (sample 1) (sample 2)Copies (ng) (ng) RNA Subcutaneous 60.2785303 73.59679955 66.94 3.0616.34 1093.75 Adipocytes Zenbio Subcutaneous Adipose 3.0325729651.985862153 2.51 0.96 52.36 131.37 Zenbio Adrenal Gland 0.9657034970.965703497 0.97 0.61 81.97 79.16 Clontech Whole Brain Clontech4131.557992 6997.879078 5564.72 7.24 6.91 38430.38 Fetal Brain Clontech0.965703497 3.268211325 2.12 0.48 103.95 220.06 Cerebellum Clontech3.301057867 17.3966665 10.35 2.17 23.04 238.45 Cervix 5.9204840497.517891571 6.72 2.42 20.66 138.83 Colon 35.48962684 22.53180605 29.012.71 18.45 535.25 Endometrium 11.59757492 0.965703497 6.28 0.73 68.21428.49 Esophagus 7.098528857 3.523216475 5.31 1.37 36.50 193.83 HeartClontech 0.965703497 5.368977287 3.17 1.32 37.88 119.98 Hypothalamus0.965703497 0.965703497 0.97 0.32 155.28 149.95 Ileum 30.8100684714.15032296 22.48 2.58 19.38 435.66 Jejunum 44.08994058 30.2938631437.19 6.60 7.58 281.76 Kidney 9.424973981 15.68529125 12.56 2.12 23.58296.11 Liver 3.742288161 0.965703497 2.35 1.50 33.33 78.47 Fetal LiverClontech 94.45949484 93.8962252 94.18 10.40 4.81 452.78 Lung 13.8478244419.95367566 16.90 2.57 19.46 328.81 Mammary Gland 107.795616195.02632495 101.41 13.00 3.85 390.04 Clontech Myometrium 12.5011786614.93742804 13.72 2.34 21.37 293.15 Omentum 13.998213 22.03816357 18.023.94 12.69 228.66 Ovary 0.965703497 0.965703497 0.97 4.34 11.52 11.13Pancreas 2.254750425 0.965703497 1.61 0.81 61.80 99.52 Head of Pancreas0.965703497 0.965703497 0.97 1.57 31.85 30.75 Parotid Gland 25.893089214.85668173 20.37 5.48 9.12 185.90 Placenta Clontech 83.8402966895.02632495 89.43 5.26 9.51 850.13 Prostate 8.047386733 15.1824526211.61 3.00 16.67 193.58 Rectum 10.53572882 20.06385011 15.30 1.23 40.65621.94 Salivary Gland 62.43024331 57.19623352 59.81 7.31 6.84 409.12Clontech Skeletal Muscle 1.376746214 0.965703497 1.17 1.26 39.68 46.48Clontech Skin 0.965703497 0.965703497 0.97 1.21 41.32 39.91 SmallIntestine 0.965703497 0.965703497 0.97 0.98 51.07 49.32 Clontech Spleen0.965703497 5.740147492 3.35 4.92 10.16 34.07 Stomach 0.9657034970.965703497 0.97 2.73 18.32 17.69 Testis Clontech 0.9657034970.965703497 0.97 0.57 87.87 84.86 Thymus Clontech 258.7386545207.7169358 233.23 9.89 5.06 1179.11 Thyroid 12.56849785 19.0948934315.83 2.77 18.05 285.77 Trachea Clontech 24.35330878 31.87047641 28.119.71 5.15 144.76 Urinary Bladder 51.81831091 57.53035871 54.67 5.47 9.14499.77 Uterus 13.12099559 14.61718971 13.87 5.34 9.36 129.86 copies ofmRNA Reg detected/ number 50 ng Fold Change Sample (GSK Mean GOI totalin Disease sbg417005LAMININ identifier) copies RNA Sample Populationcolon normal GW98-167 21941 15446.92728 30893.85 colon normal colontumor GW98-166 21940 23910.90415 47821.81 colon tumor 1.547939193 colonnormal GW98-178 22080 14621.97321 29243.95 colon normal colon tumorGW98-177 22060 2058.30396 4116.61 colon tumor −7.10389403 colon normalGW98-561 23514 5590.900474 11181.80 colon normal colon tumor GW98-56023513 12318.10362 24636.21 colon tumor 2.203241442 colon normal GW98-89424691 4478.692403 8957.38 colon normal colon tumor GW98-893 246907546.100944 15092.20 colon tumor 1.684889308 lung normal GW98-3 2074223910.90415 47821.81 lung normal lung tumor GW98-2 20741 35021.2331770042.47 lung tumor 1.464655328 lung normal GW97-179 20677 23341.6142146683.23 lung normal lung tumor GW97-178 20676 24103.90252 48207.81 lungtumor 1.032657909 lung normal GW98-165 21922 18374.41273 36748.83 lungnormal lung tumor GW98-164 21921 34735.19726 69470.39 lung tumor1.890411289 lung normal GW98-282 22584 3002.298467 6004.60 lung normallung tumor GW98-281 22583 3519.560955 7039.12 lung tumor 1.172288829breast normal GW00-392 28750 5978.671937 5978.67 breast normal breasttumor GW00-391 28746 5674.721186 11349.44 breast tumor 1.898321649breast normal GW00-413 28798 1523.643258 1523.64 breast normal breasttumor GW00-412 28797 956.0902914 1912.18 breast tumor 1.255005444 breastnormal GW00- 27592-95 760.6128764 760.61 breast 235:238 normal breasttumor GW00- 27588-91 4192.50003 4192.50 breast tumor 5.51200244 231:234breast normal GW98-621 23656 5674.721186 11349.44 breast normal breasttumor GW98-620 23655 8017.202071 16034.40 breast tumor 1.412792243 brainnormal BB99-542 25507 791.7818289 1583.56 brain normal brain normalBB99-406 25509 524.990001 1049.98 brain normal brain normal BB99-90425546 396.8655236 793.73 brain normal brain stage 5 ALZ BB99- 255023203.498645 6407.00 brain stage 5 5.608243725 874 ALZ brain stage 5 ALZBB99- 25503 3925.505917 7851.01 brain stage 5 6.872234505 887 ALZ brainstage 5 ALZ BB99- 25504 1502.651942 3005.30 brain stage 5 2.630635833862 ALZ brain stage 5 ALZ BB99- 25542 1555.711325 3111.42 brain stage 52.723524884 927 ALZ CT lung KC normal 3730.249874 7460.50 CT lung lung26 KC normal 286.3143862 286.31 lung 26 lung 27 KC normal 72.3056094172.31 lung 27 lung 24 KC COPD 28.47771374 28.48 lung 24 −69.25877363lung 28 KC COPD 66.98006875 66.98 lung 28 −29.44654382 lung 23 KC COPD57.53035871 57.53 lung 23 −34.28331708 lung 25 KC COPD 70.20637402 70.21lung 25 asthmatic lung 29321 2304.915385 2304.92 asthmatic 1.168624722ODO3112 lung asthmatic lung 29323 3112.377018 6224.75 asthmatic3.156038395 ODO3433 lung asthmatic lung 29322 21892.2071 43784.41asthmatic 22.19931768 ODO3397 lung asthmatic lung 29325 5268.43836410536.88 asthmatic 5.34234563 ODO4928 lung endo cells KC control396.8655236 396.87 endo cells endo VEGF KC 157.1987188 157.20 endo VEGF−2.524610421 endo bFGF KC 518.1542863 518.15 endo bFGF 1.305616778 heartClontech normal 1865.302957 3730.61 heart heart (T-1) ischemic 294173757.505456 7515.01 heart T-1 2.014421005 heart (T-14) non- 294221633.333543 3266.67 heart T-14 −1.142022072 obstructive DCM heart(T-3399) DCM 29426 2938.226492 5876.45 heart T-3399 1.575200683 adenoidGW99-269 26162 1238.725105 2477.45 adenoid tonsil GW98-280 225822288.625236 4577.25 tonsil T cells PC00314 28453 61.34444995 122.69 Tcells PBMNC KC 5.341492957 5.34 PBMNC monocyte KC 3.576686692 7.15monocyte B cells PC00665 28455 716.2601536 1432.52 B cells dendriticcells 28441 32.23243314 64.46 dendritic cells neutrophils 2844032.9693996 32.97 neutrophils eosinophils 28446 1.444144312 2.89eosinophils BM unstim KC 5.951115795 5.95 BM unstim BM stim KC11.72233235 11.72 BM stim 1.969770503 osteo dif KC 10.20495465 10.20osteo dif osteo undif KC 8.526098078 8.53 osteo undif −1.196907959chondrocytes 14621.97321 36554.93 chondrocytes OA Synovium IP12/01 294625549.480142 5549.48 OA Synovium OA Synovium NP10/01 29461 3545.1971277090.39 OA Synovium OA Synovium NP57/00 28464 4223.325454 8446.65 OASynovium RA Synovium NP03/01 28466 1221.845309 2443.69 RA Synovium RASynovium NP71/00 28467 4892.67872 9785.36 RA Synovium RA SynoviumNP45/00 28475 1080.396739 2160.79 RA Synovium OA bone (biobank) 29217995.7612933 995.76 OA bone (biobank) OA bone Sample 1 J. Emory982.3483914 1964.70 OA bone OA bone Sample 2 J. Emory 472.8535333 945.71OA bone Cartilage (pool) Normal 1213.496434 2426.99 Cartilage (pool)Cartilage (pool) OA 697.4302173 1394.86 Cartilage −1.73995391 (pool) PBLunifected 28441 161.1142664 322.23 PBL unifected PBL HIV IIIB 28442191.5686557 383.14 PBL HIV 1.189023542 IIIB MRC5 uninfected 291585934.220593 11868.44 MRC5 (100%) uninfected (100%) MRC5 HSV strain F29178 50.63206269 101.26 MRC5 HSV −117.2028213 strain F W12 cells 2917913843.2955 27686.59 W12 cells Keratinocytes 29180 11849.9156 23699.83Keratinocytes

[0130] Gene Name sbg417005LAMININ Fold Change in Disease PopulationRelative to Disease tissues Normal colon tumor 1.55 colon tumor −7.10colon tumor 2.20 colon tumor 1.68 lung tumor 1.46 lung tumor 1.03 lungtumor 1.89 lung tumor 1.17 breast tumor 1.90 breast tumor 1.26 breasttumor 5.51 breast tumor 1.41 brain stage 5 ALZ 5.61 brain stage 5 ALZ6.87 brain stage 5 ALZ 2.63 brain stage 5 ALZ 2.72 lung 24 −69.26 lung28 −29.45 lung 23 −34.28 asthmatic lung 1.17 asthmatic lung 3.16asthmatic lung 22.20 asthmatic lung 5.34 endo VEGF −2.52 endo bFGF 1.31heart T-1 2.01 heart T-14 −1.14 heart T-3399 1.58 BM stim 1.97 osteoundif −1.20 Cartilage (pool) −1.74 PBL HIV IIIB 1.19 MRC5 HSV strain F−117.20

[0131] Gene Name sbg425649KINASEa

[0132] Strongly expressed in neutrophils and eosinophils suggestingfunction in immune system such as involvement in allergic reactions andanti-infective. Lower expression in T-cells. Expression in 2/3 OA bonesamples indicate a role in OA. Strongly expressed in rectum and skeletalmuscle, unknown function. copies of mRNA 50 detected/ Mean GOI Mean GOIAverage 18S ng/18S 50 ng Sample copies copies GOI rRNA rRNA totalsbg425649KINASEa (sample 1) (sample 2) Copies (ng) (ng) RNA Subcutaneous0.00 0.03 0.02 3.06 16.34 0.25 Adipocytes Zenbio Subcutaneous Adipose0.00 0.00 0.00 0.96 52.36 0.00 Zenbio Adrenal Gland Clontech 0.23 0.000.12 0.61 81.97 9.43 Whole Brain Clontech 163.64 47.63 105.64 7.24 6.91729.52 Fetal Brain Clontech 0.47 0.00 0.24 0.48 103.95 24.43 CerebellumClontech 0.00 0.00 0.00 2.17 23.04 0.00 Cervix 5.54 0.00 2.77 2.42 20.6657.23 Colon 0.70 0.00 0.35 2.71 18.45 6.46 Endometrium 0.33 0.06 0.200.73 68.21 13.30 Esophagus 0.35 0.47 0.41 1.37 36.50 14.96 HeartClontech 0.00 0.00 0.00 1.32 37.88 0.00 Hypothalamus 0.00 0.00 0.00 0.32155.28 0.00 Ileum 0.00 4.49 2.25 2.58 19.38 43.51 Jejunum 0.29 0.73 0.516.60 7.58 3.86 Kidney 0.00 0.00 0.00 2.12 23.58 0.00 Liver 10.48 5.648.06 1.50 33.33 268.67 Fetal Liver Clontech 8.56 0.00 4.28 10.40 4.8120.58 Lung 0.00 0.00 0.00 2.57 19.46 0.00 Mammary Gland 0.00 0.00 0.0013.00 3.85 0.00 Clontech Myometrium 8.61 5.00 6.81 2.34 21.37 145.41Omentum 0.23 10.99 5.61 3.94 12.69 71.19 Ovary 4.48 4.62 4.55 4.34 11.5252.42 Pancreas 0.27 0.00 0.14 0.81 61.80 8.34 Head of Pancreas 0.11 0.040.08 1.57 31.85 2.39 Parotid Gland 0.69 4.51 2.60 5.48 9.12 23.72Placenta Clontech 10.58 0.14 5.36 5.26 9.51 50.95 Prostate 9.74 6.187.96 3.00 16.67 132.67 Rectum 225.51 76.99 151.25 1.23 40.65 6148.37Salivary Gland 60.93 67.22 64.08 7.31 6.84 438.27 Clontech SkeletalMuscle 749.28 29.78 389.53 1.26 39.68 15457.54 Clontech Skin 0.00 4.462.23 1.21 41.32 92.15 Small Intestine 0.73 0.00 0.37 0.98 51.07 18.64Clontech Spleen 4.10 8.60 6.35 4.92 10.16 64.53 Stomach 4.24 19.28 11.762.73 18.32 215.38 Testis Clontech 10.11 6.34 8.23 0.57 87.87 722.76Thymus Clontech 2.79 5.35 4.07 9.89 5.06 20.58 Thyroid 0.00 0.06 0.032.77 18.05 0.54 Trachea Clontech 5.24 14.14 9.69 9.71 5.15 49.90 UrinaryBladder 0.09 0.00 0.05 5.47 9.14 0.41 Uterus 27.26 7.61 17.44 5.34 9.36163.25 copies of mRNA Reg detected/ number Mean 50 ng Fold Change Sample(GSK GOI total in Disease sbg425649KINASEa identifier) copies RNA SamplePopulation colon normal GW98-167 21941 11.11 22.22 colon normal colontumor GW98-166 21940 7.3 14.60 colon tumor −1.521917808 colon normalGW98-178 22080 0 0.00 colon normal colon tumor GW98-177 22060 2.57 5.14colon tumor 5.14 colon normal GW98-561 23514 0 0.00 colon normal colontumor GW98-560 23513 0 0.00 colon tumor 0 colon normal GW98-894 246912.71 5.42 colon normal colon tumor GW98-893 24690 8.51 17.02 colon tumor3.140221402 lung normal GW98-3 20742 1.78 3.56 lung normal lung tumorGW98-2 20741 0 0.00 lung tumor −3.56 lung normal GW97-179 20677 3.186.36 lung normal lung tumor GW97-178 20676 2.64 5.28 lung tumor−1.204545455 lung normal GW98-165 21922 6.46 12.92 lung normal lungtumor GW98-164 21921 19.99 39.98 lung tumor 3.094427245 lung normalGW98-282 22584 31.56 63.12 lung normal lung tumor GW98-281 22583 7.4714.94 lung tumor −4.224899598 breast normal GW00-392 28750 5.68 5.68breast normal breast tumor GW00-391 28746 2.87 5.74 breast tumor1.01056338 breast normal GW00-413 28798 1.66 1.66 breast normal breasttumor GW00-412 28797 1.99 3.98 breast tumor 2.397590361 breast normalGW00- 27592-95 0 0.00 breast 235:238 normal breast tumor GW00- 27588-912.19 2.19 breast tumor 2.19 231:234 breast normal GW98-621 23656 4.729.44 breast normal breast tumor GW98-620 23655 0 0.00 breast tumor −9.44brain normal BB99-542 25507 28.9 57.80 brain normal brain normalBB99-406 25509 24.84 49.68 brain normal brain normal BB99-904 25546 6.9213.84 brain normal brain stage 5 ALZBB99- 25502 23.65 47.30 brain stage5 1.169634026 874 ALZ brain stage 5 ALZ BB99- 25503 28.68 57.36 brainstage 5 1.418397626 887 ALZ brain stage 5 ALZ BB99- 25504 18.18 36.36brain stages 5 −1.112211221 862 ALZ brain stage 5 ALZ BB99- 25542 14.1828.36 brain stage 5 −1.425952045 927 ALZ CT lung KC normal 29.45 58.90CT lung lung 26 KC normal 2.47 2.47 lung 26 lung 27 KC normal 0 0.00lung 27 lung 24 KC COPD 0 0.00 lung 24 −15.3425 lung 28 KC COPD 0.3 0.30lung 28 −51.14166667 lung 23 KC COPD 0 0.00 lung 23 −15.3425 lung 25 KCCOPD 0 0.00 lung 25 asthmatic lung 29321 3.24 3.24 asthmatic−4.735339506 ODO3112 lung asthmatic lung 29323 88.32 176.64 asthmatic11.51311716 ODO3433 lung asthmatic lung 29322 55.65 111.30 asthmatic7.254358807 ODO3397 lung asthmatic lung 29325 50.64 101.28 asthmatic6.601270979 ODO4928 lung endo cells KC control 0 0.00 endo cells endoVEGF KC 0 0.00 endo VEGF 0 endo bFGF KC 0 0.00 endo bFGF 0 heartClontech normal 15.26 30.52 heart heart (T-1 ) ischemic 29417 0 0.00heart T-1 −30.52 heart (T-14) non- 29422 3.69 7.38 heart T-14−4.135501355 obstructive DCM heart (T-3399) DCM 29426 0 0.00 heartT-3399 −30.52 adenoid GW99-269 26162 0 0.00 adenoid tonsil GW98-28022582 3.65 7.30 tonsil T cells PC00314 28453 167.51 335.02 T cells PBMNCKC 2.5 2.50 PBMNC monocyte KC 2.37 4.74 monocyte B cells PC00665 28455 00.00 B cells dendritic cells 28441 0 0.00 dendritic cells neutrophils28440 1576.76 1576.76 neutrophils eosinophils 28446 755.1 1510.20eosinophils BM unstim KC 14.87 14.87 BM unstim BM stim KC 45.45 45.45 BMstim 3.056489576 osteo dif KC 0 0.00 osteo dif osteo undif KC 0 0.00osteo undif 0 chondrocytes 7.48 18.70 chondrocytes OA Synovium IP12/0129462 17.79 17.79 OA Synovium OA Synovium NP10/01 29461 14.09 28.18 OASynovium OA Synovium NP57/00 28464 11.97 23.94 OA Synovium RA SynoviumNP03/01 28466 6.84 13.68 RA Synovium RA Synovium NP71/00 28467 22.8845.76 RA Synovium RA Synovium NP45/00 28475 1.64 3.28 RA Synovium OAbone (biobank) 29217 370.22 370.22 OA bone (biobank) OA bone Sample 1 J.Emory 3.21 6.42 OA bone OA bone Sample 2 J. Emory 311.65 623.30 OA boneCartilage (pool) Normal 32.23 64.46 Cartilage (pool) Cartilage (pool) OA2.87 5.74 Cartilage −11.22996516 (pool) PBL unifected 28441 4.18 8.36PBL unifected PBL HIV IIIB 28442 0 0.00 PBL HIV −8.36 IIIB MRC5uninfected 29158 4.4 8.80 MRC5 (100%) uninfected (100%) MRC5 HSV strainF 29178 11.46 22.92 MRC5 HSV 2.604545455 strain F W12 cells 29179 0 0.00W12 cells Keratinocytes 29180 0 0.00 Keratinocytes

[0133] Gene Name sbg425649KINASEa Fold Change in Disease PopulationRelative to Disease tissues Normal colon tumor −1.52 colon tumor 5.14colon tumor 0.00 colon tumor 3.14 lung tumor −3.56 lung tumor −1.20 lungtumor 3.09 lung tumor −4.22 breast tumor 1.01 breast tumor 2.40 breasttumor 2.19 breast tumor −9.44 brain stage 5 ALZ 1.17 brain stage 5 ALZ1.42 brain stage 5 ALZ −1.11 brain stage 5 ALZ −1.43 lung 24 −15.34 lung28 −51.14 lung 23 −15.34 asthmatic lung −4.74 asthmatic lung 11.51asthmatic lung 7.25 asthmatic lung 6.60 endo VEGF 0.00 endo bFGF 0.00heart T-1 −30.52 heart T-14 −4.14 heart T-3399 −30.52 BM stim 3.06 osteoundif 0.00 Cartilage (pool) −11.23 PBL HIV IIIB −8.36 MRC5 HSV strain F2.60

[0134] Gene Name sbg419582PROTOCADHERIN

[0135] Brain specific expression. No correlation with Alzheimer'sdisease. Low expression in RA and OA synovium but no corroboratingexpression in immune cells. Slightly upregulated in heart disease.Overexpressed in lung (1/4) and breast (1/4) tumors. copies of mRNA 50ng/ detected/ Sample Mean GOI Mean GOI Average 18S 18S 50 ngsbg419582PROTOCA copies copies GOI rRNA rRNA total DHERIN (sample 1)(sample 2) Copies (ng) (ng) RNA Subcutaneous 18.18 23.43 20.81 3.0616.34 339.95 Adipocytes Zenbio Subcutaneous Adipose 0.11 0.33 0.22 0.9652.36 11.52 Zenbio Adrenal Gland Clontech 1.8 1.06 1.43 0.61 81.97117.21 Whole Brain Clontech 10913.92 10314.42 10614.17 7.24 6.9173302.28 Fetal Brain Clontech 0.31 4.68 2.50 0.48 103.95 259.36Cerebellum Clontech 0.1 4.58 2.34 2.17 23.04 53.92 Cervix 0.22 1.22 0.722.42 20.66 14.88 Colon 0.31 13.73 7.02 2.71 18.45 129.52 Endometrium 0.10.58 0.34 0.73 68.21 23.19 Esophagus 2.21 1.96 2.09 1.37 36.50 76.09Heart Clontech 0.32 0 0.16 1.32 37.88 6.06 Hypothalamus 0.15 1.2 0.680.32 155.28 104.81 Ileum 2.77 1.03 1.90 2.58 19.38 36.82 Jejunum 0.261.18 0.72 6.60 7.58 5.45 Kidney 1.99 0.28 1.14 2.12 23.58 26.77 Liver7.59 12.42 10.01 1.50 33.33 333.50 Fetal Liver Clontech 18.75 11.0414.90 10.40 4.81 71.61 Lung 7.19 0.71 3.95 2.57 19.46 76.85 MammaryGland 88.14 97.88 93.01 13.00 3.85 357.73 Clontech Myometrium 0.51 4.82.66 2.34 21.37 56.73 Omentum 7.52 2.19 4.86 3.94 12.69 61.61 Ovary13.46 4.84 9.15 4.34 11.52 105.41 Pancreas 0.49 1.02 0.76 0.81 61.8046.66 Head of Pancreas 0.29 0.15 0.22 1.57 31.85 7.01 Parotid Gland 6.096.19 6.14 5.48 9.12 56.02 Placenta Clontech 10.67 2.35 6.51 5.26 9.5161.88 Prostate 2.02 3.59 2.81 3.00 16.67 46.75 Rectum 0.54 7.25 3.901.23 40.65 158.33 Salivary Gland 20.51 13.73 17.12 7.31 6.84 117.10Clontech Skeletal Muscle 1.06 0.79 0.93 1.26 39.68 36.71 Clontech Skin13.09 0.6 6.85 1.21 41.32 282.85 Small Intestine 0.11 2.47 1.29 0.9851.07 65.88 Clontech Spleen 1.05 11 6.03 4.92 10.16 61.23 Stomach 0.951.3 1.13 2.73 18.32 20.60 Testis Clontech 2.82 3.19 3.01 0.57 87.87264.06 Thymus Clontech 117.82 118.81 118.32 9.89 5.06 598.15 Thyroid2.34 2.29 2.32 2.77 18.05 41.79 Trachea Clontech 8.72 9.37 9.05 9.715.15 46.58 Urinary Bladder 14.23 16.82 15.53 5.47 9.14 141.91 Uterus1.49 27.26 14.38 5.34 9.36 134.60 copies of Reg mRNA Sample number Meandetected/50 ng Fold Change in sbg419582PROTOCA (GSK GOI total DiseaseDHERIN identifier) copies RNA Sample Population colon normal GW98-16721941 464.48 928.96 colon normal colon tumor GW98-166 21940 84.22 168.44colon tumor −5.515079554 colon normal GW98-178 22080 32.8 65.60 colonnormal colon tumor GW98-177 22060 44.71 89.42 colon tumor 1.363109756colon normal GW98-561 23514 135.5 271.00 colon normal colon tumorGW98-560 23513 78.51 157.02 colon tumor −1.72589479 colon normalGW98-894 24691 454.16 908.32 colon normal colon tumor GW98-893 2469051.37 102.74 colon tumor −8.840957757 lung normal GW98-3 20742 60.35120.70 lung normal lung tumor GW98-2 20741 101.98 203.96 lung tumor1.689809445 lung normal GW97-179 20677 264 528.00 lung normal lung tumorGW97-178 20676 78.49 156.98 lung tumor −3.363485794 lung normal GW98-16521922 88.19 176.38 lung normal lung tumor GW98-164 21921 7554.5815109.16 lung tumor 85.66254677 lung normal GW98-282 22584 344.2 688.40lung normal lung tumor GW98-281 22583 45.51 91.02 lung tumor−7.563172929 breast normal GW00-392 28750 132.43 132.43 breast normalbreast tumor GW00-391 28746 98.14 196.28 breast tumor 1.482141509 breastnormal GW00-413 28798 154.37 154.37 breast normal breast tumor GW00-41228797 1289.09 2578.18 breast tumor 16.70130207 breast normal GW00-27592-95 18.63 18.63 breast 235:238 normal breast tumor GW00- 27588-91133.52 133.52 breast tumor 7.166935051 231:234 breast normal GW98-62123656 1334.91 2669.82 breast normal breast tumor GW98-620 23655 212.39424.78 breast tumor −6.285182918 brain normal BB99-542 25507 6816.4713632.94 brain normal brain normal BB99-406 25509 1984.48 3968.96 brainnormal brain normal BB99-904 25546 2805.82 5611.64 brain normal brainstage 5 ALZ BB99- 25502 467.59 935.18 brain stage 5 −8.274178946 874 ALZbrain stage 5 ALZ BB99- 25503 3104.22 6208.44 brain stage 5 −1.24634315887 ALZ brain stage 5 ALZ BB99- 25504 1889.81 3779.62 brain stage 5−2.047255191 862 ALZ brain stage 5 ALZ BB99- 25542 2902.29 5804.58 brainstage 5 −1.333058837 927 ALZ CT lung KC normal 103.32 206.64 CT lunglung 26 KC normal 1.13 1.13 lung 26 lung 27 KC normal 1.51 1.51 lung 27lung 24 KC COPD 1.47 1.47 lung 24 −35.82312925 lung 28 KC COPD 0 0.00lung 28 −52.66 lung 23 KC COPD 1.91 1.91 lung 23 −27.57068063 lung 25 KCCOPD 1.36 1.36 lung 25 asthmatic lung 29321 2.68 2.68 asthmatic−19.64925373 ODO3112 lung asthmatic lung 29323 3.25 6.50 asthmatic−8.101538462 ODO3433 lung asthmatic lung 29322 26.23 52.46 asthmatic−1.003812429 ODO3397 lung asthmatic lung 29325 7.15 14.30 asthmatic−3.682517483 ODO4928 lung endo cells KC control 15.9 15.90 endo cellsendo VEGF KC 8.26 8.26 endo VEGF −1.924939467 endo bFGF KC 2.01 2.01endo bFGF −7.910447761 heart Clontech normal 7.9 15.80 heart heart (T-1)ischemic 29417 67.47 134.94 heart T-1 8.540506329 heart (T-14) non-29422 106.83 213.66 heart T-14 13.52278481 obstructive DCM heart(T-3399) DCM 29426 425.28 850.56 heart T-3399 53.83291139 adenoidGW99-269 26162 15.98 31.96 adenoid tonsil GW98-280 22582 17.95 35.90tonsil T cells PC00314 28453 3.18 6.36 T cells PBMNC KC 0 0.00 PBMNCmonocyte KC 0.81 1.62 monocyte B cells PC00665 28455 2.74 5.48 B cellsdendritic cells 28441 0 0.00 dendritic cells neutrophils 28440 0 0.00neutrophils eosinophils 28446 0 0.00 eosinophils BM unstim KC 0 0.00 BMunstim BM stim KC 0 0.00 BM stim 0 osteo dif KC 2.34 2.34 osteo difosteo undif KC 0 0.00 osteo undif −2.34 chondrocytes 145.14 362.85chondrocytes OA Synovium IP12/01 29462 320.78 320.78 OA Synovium OASynovium NP10/01 29461 396.85 793.70 OA Synovium OA Synovium NP57/0028464 329.87 659.74 OA Synovium RA Synovium NP03/01 28466 103.85 207.70RA Synovium RA Synovium NP71/00 28467 617.72 1235.44 RA Synovium RASynovium NP45/00 28475 63.13 126.26 RA Synovium OA bone (biobank) 292173.19 3.19 OA bone (biobank) OA bone Sample 1 J. Emory 126.87 253.74 OAbone OA bone Sample 2 J. Emory 44.76 89.52 OA bone Cartilage (pool)Normal 502.66 1005.32 Cartilage (pool) Cartilage (pool) OA 206.76 413.52Cartilage −2.431127878 (pool) PBL unifected 28441 0 0.00 PBL unifectedPBL HIV IIIB 28442 0 0.00 PBL HIV 0 IIIB MRC5 uninfected 29158 0 0.00MRC5 (100%) uninfected (100%) MRC5 HSV strain F 29178 17.73 35.46 MRC5HSV 35.46 strain F W12 cells 29179 0.62 1.24 W12 cells Keratinocytes29180 22.63 45.26 Keratinocytes

[0136] Gene Name sbg419582PROTOCADHERIN Fold Change in DiseasePopulation Relative to Disease tissues Normal colon tumor −5.52 colontumor 1.36 colon tumor −1.73 colon tumor −8.84 lung tumor 1.69 lungtumor −3.36 lung tumor 85.66 lung tumor −7.56 breast tumor 1.48 breasttumor 16.70 breast tumor 7.17 breast tumor −6.29 brain stage 5 ALZ −8.27brain stage 5 ALZ −1.25 brain stage 5 ALZ −2.05 brain stage 5 ALZ −1.33lung 24 −35.82 lung 28 −52.66 lung 23 −27.57 asthmatic lung −19.65asthmatic lung −8.10 asthmatic lung −1.00 asthmatic lung −3.68 endo VEGF−1.92 endo bFGF −7.91 heart T-1 8.54 heart T-14 13.52 heart T-3399 53.83BM stim 0.00 osteo undif −2.34 Cartilage (pool) −2.43 PBL HIV IIIB 0.00MRC5 HSV strain F 35.46

[0137] Gene Name sbg453915TECTORINa

[0138] Very low expression overall. Expression in female reproductivetissues suggests a protein that may be secreted by these tissue types.copies of mRNA detected/ Mean GOI Mean GOI Average 18S 50 ng/18S 50 ngSample copies copies GOI rRNA rRNA total sbg453915TECTORINa (sample 1)(sample 2) Copies (ng) (ng) RNA Subcutaneous 2.70 5.41 4.06 3.06 16.3466.26 Adipocytes Zenbio Subcutaneous Adipose 0.00 0.00 0.00 0.96 52.360.00 Zenbio Adrenal Gland Clontech 3.75 5.67 4.71 0.61 81.97 386.07Whole Brain Clontech 22.57 27.88 25.23 7.24 6.91 174.21 Fetal BrainClontech 2.42 1.80 2.11 0.48 103.95 219.33 Cerebellum Clontech 0.00 1.930.97 2.17 23.04 22.24 Cervix 2.90 2.10 2.50 2.42 20.66 51.65 Colon 11.192.68 6.94 2.71 18.45 127.95 Endometrium 4.79 19.31 12.05 0.73 68.21821.96 Esophagus 2.06 2.93 2.50 1.37 36.50 91.06 Heart Clontech 5.427.31 6.37 1.32 37.88 241.10 Hypothalamus 0.00 3.70 1.85 0.32 155.28287.27 Ileum 3.72 18.75 11.24 2.58 19.38 217.73 Jejunum 28.49 49.8039.15 6.60 7.58 296.55 Kidney 2.12 4.37 3.25 2.12 23.58 76.53 Liver15.74 39.80 27.77 1.50 33.33 925.67 Fetal Liver Clontech 27.96 26.1427.05 10.40 4.81 130.05 Lung 0.00 2.37 1.19 2.57 19.46 23.05 MammaryGland 19.68 19.22 19.45 13.00 3.85 74.81 Clontech Myometrium 3.40 1.712.56 2.34 21.37 54.59 Omentum 14.33 138.99 76.66 3.94 12.69 972.84 Ovary46.55 37.80 42.18 4.34 11.52 485.89 Pancreas 4.26 2.19 3.23 0.81 61.80199.32 Head of Pancreas 1.93 1.52 1.73 1.57 31.85 54.94 Parotid Gland4.04 5.93 4.99 5.48 9.12 45.48 Placenta Clontech 3.69 15.48 9.59 5.269.51 91.11 Prostate 7.94 28.75 18.35 3.00 16.67 305.75 Rectum 11.09 3.417.25 1.23 40.65 294.72 Salivary Gland 0.00 1.45 0.73 7.31 6.84 4.96Clontech Skeletal Muscle 4.76 0.00 2.38 1.26 39.68 94.44 Clontech Skin0.00 1.39 0.70 1.21 41.32 28.72 Small Intestine 2.20 1.41 1.81 0.9851.07 92.19 Clontech Spleen 7.15 8.12 7.64 4.92 10.16 77.59 Stomach 1.980.00 0.99 2.73 18.32 18.13 Testis Clontech 6.83 2.61 4.72 0.57 87.87414.76 Thymus Clontech 0.00 0.00 0.00 9.89 5.06 0.00 Thyroid 2.38 1.882.13 2.77 18.05 38.45 Trachea Clontech 1.71 9.25 5.48 9.71 5.15 28.22Urinary Bladder 3.72 8.22 5.97 5.47 9.14 54.57 Uterus 74.31 73.54 73.935.34 9.36 692.18 copies of Reg mRNA number Mean detected/50 ng FoldChange in Sample (GSK GOI total Disease sbg453915TECTORINa identifier)copies RNA Sample Population colon normal GW98-167 21941 131.15 262.30colon normal colon tumor GW98-166 21940 85.76 171.52 colon tumor−1.529267724 colon normal GW98-178 22080 1.82 3.64 colon normal colontumor GW98-177 22060 10.14 20.28 colon tumor 5.571428571 colon normalGW98-561 23514 14.25 28.50 colon normal colon tumor GW98-560 23513 9.8919.78 colon tumor −1.440849343 colon normal GW98-894 24691 32.05 64.10colon normal colon tumor GW98-893 24690 53.06 106.12 colon tumor1.655538222 lung normal GW98-3 20742 6.9 13.80 lung normal lung tumorGW98-2 20741 0.81 1.62 lung tumor −8.518518519 lung normal GW97-17920677 1.19 2.38 lung normal lung tumor GW97-178 20676 0 0.00 lung tumor−2.38 lung normal GW98-165 21922 0.91 1.82 lung normal lung tumorGW98-164 21921 5.99 11.98 lung tumor 6.582417582 lung normal GW98-28222584 5.93 11.86 lung normal lung tumor GW98-281 22583 1.54 3.08 lungtumor −3.850649351 breast normal GW00-392 28750 6.88 6.88 breast normalbreast tumor GW00-391 28746 4.24 8.48 breast tumor 1.23255814 breastnormal GW00-413 28798 0 0.00 breast normal breast tumor GW00-412 2879713.96 27.92 breast tumor 27.92 breast normal GW00- 27592-95 14.42 14.42breast 235:238 normal breast tumor GW00- 27588-91 0 0.00 breast tumor−14.42 231:234 breast normal GW98-621 23656 5.81 11.62 breast normalbreast tumor GW98-620 23655 0 0.00 breast tumor −11.62 brain normalBB99-542 25507 20.59 41.18 brain normal brain normal BB99-406 2550915.98 31.96 brain normal brain normal BB99-904 25546 2.38 4.76 brainnormal brain stage 5 ALZ BB99- 25502 25.45 50.90 brain stage 51.960205392 874 ALZ brain stage 5 ALZ BB99- 25503 35.78 71.56 brainstage 5 2.755840822 887 ALZ brain stage 5 ALZ BB99- 25504 13.83 27.66brain stage 5 1.06521181 862 ALZ brain stage 5 ALZ BB99- 25542 21.6743.34 brain stage 5 1.669062901 927 ALZ CT lung KC normal 6.52 13.04 CTlung lung 26 KC normal 2.1 2.10 lung 26 lung 27 KC normal 0.84 0.84 lung27 lung 24 KC COPD 1.25 1.25 lung 24 −3.432 lung 28 KC COPD 0 0.00 lung28 −4.29 lung 23 KC COPD 1.16 1.16 lung 23 −3.698275862 lung 25 KC COPD1.18 1.18 lung 25 asthmatic lung ODO3112 29321 4.9 4.90 asthmatic1.142191142 lung asthmatic lung ODO3433 29323 0.83 1.66 asthmatic−2.584337349 lung asthmatic lung ODO3397 29322 2.46 4.92 asthmatic1.146853147 lung asthmatic lung ODO4928 29325 6 12.00 asthmatic2.797202797 lung endo cells KC control 2.52 2.52 endo cells endo VEGF KC1.28 1.28 endo VEGF −1.96875 endo bFGF KC 0 0.00 endo bFGF −2.52 heartClontech normal 0 0.00 heart heart (T-1) ischemic 29417 3.58 7.16 heartT-1 7.16 heart (T-14) non- 29422 0 0.00 heart T-14 0 obstructive DCMheart (T-3399)DCM 29426 0 0.00 heart T-3399 0 adenoid GW99-269 261622.29 4.58 adenoid tonsil GW98-280 22582 1.85 3.70 tonsil T cells PC0031428453 4.29 8.58 T cells PBMNC KC 0 0.00 PBMNC monocyte KC 3.39 6.78monocyte B cells PC00665 28455 6.04 12.08 B cells dendritic cells 284410.83 1.66 dendritic cells neutrophils 28440 34.69 34.69 neutrophilseosinophils 28446 2.86 5.72 eosinophils BM unstim KC 0 0.00 BM unstim BMstim KC 12.8 12.80 BM stim 12.8 osteo dif KC 0 0.00 osteo dif osteoundif KC 0 0.00 osteo undif 0 chondrocytes 4.78 11.95 chondrocytes OASynovium IP12/01 29462 18.31 18.31 OA Synovium OA Synovium NP10/01 294610 0.00 OA Synovium OA Synovium NP57/00 28464 11.46 22.92 OA Synovium RASynovium NP03/01 28466 0.87 1.74 RA Synovium RA Synovium NP71/00 2846726.95 53.90 RA Synovium RA Synovium NP45/00 28475 18.91 37.82 RASynovium OA bone (biobank) 29217 0 0.00 OA bone (biobank) OA bone Sample1 J. Emory 8.66 17.32 OA bone OA bone Sample 2 J. Emory 7.8 15.60 OAbone Cartilage (pool) Normal 16.93 33.86 Cartilage (pool) Cartilage(pool) OA 6.39 12.78 Cartilage −2.649452269 (pool) PBL unifected 28441 00.00 PBL unifected PBL HIV IIIB 28442 1.15 2.30 PBL HIV 2.3 IIIB MRC5uninfected 29158 0 0.00 MRC5 (100%) uninfected (100%) MRC5 HSV strain F29178 70.84 141.68 MRC5 HSV 141.68 strain F W12 cells 29179 5.59 11.18W12 cells Keratinocytes 29180 0 0.00 Keratinocytes

[0139] Gene Name sbg453915TECTORINa Fold Change in Disease PopulationRelative to Disease tissues Normal colon tumor −1.53 colon tumor 5.57colon tumor −1.44 colon tumor 1.66 lung tumor −8.52 lung tumor −2.38lung tumor 6.58 lung tumor −3.85 breast tumor 1.23 breast tumor 27.92breast tumor −14.42 breast tumor −11.62 brain stage 5 ALZ 1.96 brainstage 5 ALZ 2.76 brain stage 5 ALZ 1.07 brain stage 5 ALZ 1.67 lung 24−3.43 lung 28 −4.29 lung 23 −3.70 asthmatic lung 1.14 asthmatic lung−2.58 asthmatic lung 1.15 asthmatic lung 2.80 endo VEGF −1.97 endo bFGF−2.52 heart T-1 7.16 heart T-14 0.00 heart T-3399 0.00 BM stim 12.80osteo undif 0.00 Cartilage (pool) −2.65 PBL HIV IIIB 2.30 MRC5 HSVstrain F 141.68

[0140] Gene Name SBh385630.antiinflam

[0141] Some expression in adenoid, tonsils and T-cells suggesting a rolein the immune system. Expression in GI tissues suggests a role in thedigestive system and potential role in diseases of the GI system such asEBD. Overexpression in lung (1/4) and colon tumors (1/4) suggesting arole in lung and colon cancer. Increased expression in ischemic anddilated heart samples indicating a role in Cardiovascular diseases thatare consistent with cardiac hypertropby. Expression in whole brain butnot localized to hypothalamus, cerebellum or cortex. copies of mRNAdetected/ Mean GOI Mean GOI Average 18S 50 ng/18S 50 ng Sample copiescopies GOI rRNA rRNA total SBh385630.antiinflam (sample 1) (sample 2)Copies (ng) (ng) RNA Subcutaneous 0.00 6.41 3.21 3.06 16.34 52.37Adipocytes Zenbio Subcutaneous Adipose 0.00 0.00 0.00 0.96 52.36 0.00Zenbio Adrenal Gland Clontech 8.40 0.00 4.20 0.61 81.97 344.26 WholeBrain Clontech 817.17 466.76 641.97 7.24 6.91 4433.46 Fetal BrainClontech 3.80 0.00 1.90 0.48 103.95 197.51 Cerebellum Clontech 6.66 0.003.33 2.17 23.04 76.73 Cervix 11.99 12.30 12.15 2.42 20.66 250.93 Colon55.51 211.32 133.42 2.71 18.45 2461.53 Endometrium 0.00 0.00 0.00 0.7368.21 0.00 Esophagus 11.75 30.29 21.02 1.37 36.50 767.15 Heart Clontech0.00 0.00 0.00 1.32 37.88 0.00 Hypothalamus 0.00 0.00 0.00 0.32 155.280.00 Ileum 40.37 42.85 41.61 2.58 19.38 806.40 Jejunum 200.19 263.82232.01 6.60 7.58 1757.61 Kidney 18.38 34.53 26.46 2.12 23.58 623.94Liver 11.00 17.20 14.10 1.50 33.33 470.00 Fetal Liver Clontech 150.74123.93 137.34 10.40 4.81 660.26 Lung 82.73 77.24 79.99 2.57 19.461556.13 Mammary Gland 161.37 155.19 158.28 13.00 3.85 608.77 ClontechMyometrium 5.79 9.38 7.59 2.34 21.37 162.07 Omentum 36.14 46.80 41.473.94 12.69 526.27 Ovary 59.25 44.29 51.77 4.34 11.52 596.43 Pancreas6.29 6.70 6.50 0.81 61.80 401.42 Head of Pancreas 0.00 26.25 13.13 1.5731.85 417.99 Parotid Gland 8.77 52.96 30.87 5.48 9.12 281.61 PlacentaClontech 4.11 0.00 2.06 5.26 9.51 19.53 Prostate 100.91 49.99 75.45 3.0016.67 1257.50 Rectum 180.24 305.61 242.93 1.23 40.65 9875.00 SalivaryGland Clontech 49.36 70.01 59.69 7.31 6.84 408.24 Skeletal Muscle 0.000.00 0.00 1.26 39.68 0.00 Clontech Skin 18.00 3.22 10.61 1.21 41.32438.43 Small Intestine Clontech 3.90 2.55 3.23 0.98 51.07 164.71 Spleen9.67 5.60 7.64 4.92 10.16 77.59 Stomach 32.34 83.60 57.97 2.73 18.321061.72 Testis Clontech 3.53 0.00 1.77 0.57 87.87 155.10 Thymus Clontech73.66 60.02 66.84 9.89 5.06 337.92 Thyroid 15.87 12.31 14.09 2.77 18.05254.33 Trachea Clontech 98.68 187.11 142.90 9.71 5.15 735.81 UrinaryBladder 118.92 101.91 110.42 5.47 9.14 1009.28 Uterus 9.03 24.21 16.625.34 9.36 155.62 copies of Reg mRNA number Mean detected/50 ng FoldChange in Sample (GSK GOI total Disease SBh385630.antiinflam identifier)copies RNA Sample Population colon normal GW98-167 21941 6479.7712959.54 colon normal colon tumor GW98-166 21940 7824.02 15648.04 colontumor 1.207453351 colon normal GW98-178 22080 343.81 687.62 colon normalcolon tumor GW98-177 22060 3011.93 6023.86 colon tumor 8.760449085 colonnormal GW98-561 23514 5457.38 10914.76 colon normal colon tumor GW98-56023513 4017.14 8034.28 colon tumor −1.358523726 colon normal GW98-89424691 14903.68 29807.36 colon normal colon tumor GW98-893 24690 4814.199628.38 colon tumor −3.095781429 lung normal GW98-3 20742 3731.847463.68 lung normal lung tumor GW98-2 20741 719.6 1439.20 lung tumor−5.185992218 lung normal GW97-179 20677 1090.56 2181.12 lung normal lungtumor GW97-178 20676 6187.22 12374.44 lung tumor 5.673433832 lung normalGW98-165 21922 8416.82 16833.64 lung normal lung tumor GW98-164 219214405.14 8810.28 lung tumor −1.910681613 lung normal GW98-282 225842033.26 4066.52 lung normal lung tumor GW98-281 22583 1785.69 3571.38lung tumor −1.138641086 breast normal GW00-392 28750 1583.49 1583.49breast normal breast tumor GW00-391 28746 1334.89 2669.78 breast tumor1.686010016 breast normal GW00-413 28798 1225.92 1225.92 breast normalbreast tumor GW00-412 28797 1213.71 2427.42 breast tumor 1.980080266breast normal GW00- 27592-95 862.26 862.26 breast 235:238 normal breasttumor GW00- 27588-91 1766.08 1766.08 breast tumor 2.048198919 231:234breast normal GW98-621 23656 1420.57 2841.14 breast normal breast tumorGW98-620 23655 760.05 1520.10 breast tumor −1.869048089 brain normalBB99-542 25507 679.48 1358.96 brain normal brain normal BB99-406 25509423.69 847.38 brain normal brain normal BB99-904 25546 401.34 802.68brain normal brain stage 5 ALZ BB99- 25502 264.51 529.02 brain stage 5−1.895971167 874 ALZ brain stage 5 ALZ BB99- 25503 648.88 1297.76 brainstage 5 1.293869765 887 ALZ brain stage 5 ALZ BB99- 25504 234.97 469.94brain stage 5 −2.134329205 862 ALZ brain stage 5 ALZ BB99- 25542 404.55809.10 brain stage 5 −1.239657232 927 ALZ CT lung KC normal 6620.8513241.70 CT lung lung 26 KC normal 320.43 320.43 lung 26 lung 27 KCnormal 164.59 164.59 lung 27 lung 24 KC COPD 141.57 141.57 lung 24−25.25392032 lung 28 KC COPD 323.8 323.80 lung 28 −11.04137585 lung 23KC COPD 363.35 363.35 lung 23 −9.839541764 lung 25 KC COPD 574.07 574.07lung 25 asthmatic lung 29321 6073.99 6073.99 asthmatic 1.698924325ODO3112 lung asthmatic lung 29323 4568.41 9136.82 asthmatic 2.555612662ODO3433 lung asthmatic lung 29322 17389.11 34778.22 asthmatic9.727636026 ODO3397 lung asthmatic lung 29325 4719.27 9438.54 asthmatic2.640005203 ODO4928 lung endo cells KC control 0 0.00 endo cells endoVEGF KC 0 0.00 endo VEGF 0 endo bFGF KC 0 0.00 endo bFGF 0 heartClontech normal 10.63 21.26 heart heart (T-1) ischemic 29417 599.011198.02 heart T-1 56.3508937 heart (T-14) non- 29422 666.41 1332.82heart T-14 62.69143932 obstructive DCM heart (T-3399) DCM 29426 142.85285.70 heart T-3399 13.43838194 adenoid GW99-269 26162 1138 2276.00adenoid tonsil GW98-280 22582 561.57 1123.14 tonsil T cells PC0031428453 736.27 1472.54 T cells PBMNC KC 0 0.00 PBMNC monocyte KC 30.3860.76 monocyte B cells PG00665 28455 204.15 408.30 B cells dendriticcells 28441 57.66 115.32 dendritic cells neutrophils 28440 13.3 13.30neutrophils eosinophils 28446 5.71 11.42 eosinophils BM unstim KC 0 0.00BM unstim BM stim KC 50.38 50.38 BM stim 50.38 osteo dif KC 8.62 8.62osteo dif osteo undif KC 0 0.00 osteo undif −8.62 chondrocytes 14.9837.45 chondrocytes OA Synovium IP12/01 29462 134.63 134.63 OA SynoviumOA Synovium NP10/01 29461 73.89 147.78 OA Synovium OA Synovium NP57/0028464 106.98 213.96 OA Synovium RA Synovium NP03/01 28466 26.59 53.18 RASynovium RA Synovium NP71/00 28467 60.88 121.76 RA Synovium RA SynoviumNP45/00 28475 60.81 121.62 RA Synovium OA bone (biobank) 29217 98.1898.18 OA bone (biobank) OA bone Sample 1 J. Emory 78.3 156.60 OA bone OAbone Sample 2 J. Emory 107.7 215.40 OA bone Cartilage (pool) Normal72.21 144.42 Cartilage (pool) Cartilage (pool) OA 48.61 97.22 Cartilage−1.485496811 (pool) PBL unifected 28441 30.22 60.44 PBL unifected PBLHIV IIIB 28442 21.89 43.78 PBL HIV −1.380539059 IIIB MRC5 uninfected29158 10.74 21.48 MRC5 (100%) uninfected (100%) MRC5 HSV strain F 29178171.23 342.46 MRC5 HSV 15.94320298 strain F W12 cells 29179 1143.852287.70 W12 cells Keratinocytes 29180 388.06 776.12 Keratinocytes

[0142] Gene Name SBh385630.antiinflam Fold Change in Disease PopulationRelative to Disease tissues Normal colon tumor 1.21 colon tumor 8.76colon tumor −1.36 colon tumor −3.10 lung tumor −5.19 lung tumor 5.67lung tumor −1.91 lung tumor −1.14 breast tumor 1.69 breast tumor 1.98breast tumor 2.05 breast tumor −1.87 brain stage 5 ALZ −1.90 brain stage5 ALZ 1.29 brain stage 5 ALZ −2.13 brain stage 5 ALZ −1.24 lung 24−25.25 lung 28 −11.04 lung 23 −9.84 asthmatic lung 1.70 asthmatic lung2.56 asthmatic lung 9.73 asthmatic lung 2.64 endo VEGF 0.00 endo bFGF0.00 heart T-1 56.35 heart T-14 62.69 heart T-3399 13.44 BM stim 50.38osteo undif −8.62 Cartilage (pool) −1.49 PBL HIV IIIB −1.38 MRC5 HSVstrain F 15.94

[0143] Gene Name sbg471005nAChR

[0144] Expressed in immune cells with corroborating expression in OA andRA synovium suggesting a role in this disease.

[0145] High expression in whole brain but not present in cortex,cerebellum, or hypothalamus suggesting localized brain expression.copies of mRNA detected/ Mean GOI Mean GOI Average 18S 50 ng/18S 50 ngSample copies copies GOI rRNA rRNA total sbg471005nAChR (sample 1)(sample 2) Copies (ng) (ng) RNA Subcutaneous 32.42 2.90 17.66 3.06 16.34288.56 Adipocytes Zenbio Subcutaneous Adipose 0.00 0.00 0.00 0.96 52.360.00 Zenbio Adrenal Gland Clontech 0.00 0.00 0.00 0.61 81.97 0.00 WholeBrain Clontech 1606.00 1058.07 1332.04 7.24 6.91 9199.14 Fetal BrainClontech 0.00 6.34 3.17 0.48 103.95 329.52 Cerebellum Clontech 10.650.00 5.33 2.17 23.04 122.70 Cervix 0.00 0.00 0.00 2.42 20.66 0.00 Colon0.00 0.00 0.00 2.71 18.45 0.00 Endometrium 0.00 0.00 0.00 0.73 68.210.00 Esophagus 0.00 2.52 1.26 1.37 36.50 45.99 Heart Clontech 4.05 0.002.03 1.32 37.88 76.70 Hypothalamus 2.24 0.00 1.12 0.32 155.28 173.91Ileum 0.00 0.00 0.00 2.58 19.38 0.00 Jejunum 20.32 41.44 30.88 6.60 7.58233.94 Kidney 14.56 0.00 7.28 2.12 23.58 171.70 Liver 3.55 10.72 7.141.50 33.33 237.83 Fetal Liver Clontech 127.95 116.81 122.38 10.40 4.81588.37 Lung 12.79 0.00 6.40 2.57 19.46 124.42 Mammary Gland 30.53 24.1227.33 13.00 3.85 105.10 Clontech Myometrium 0.00 7.10 3.55 2.34 21.3775.85 Omentum 8.15 0.00 4.08 3.94 12.69 51.71 Ovary 18.27 7.02 12.654.34 11.52 145.68 Pancreas 0.00 0.00 0.00 0.81 61.80 0.00 Head ofPancreas 0.00 0.00 0.00 1.57 31.85 0.00 Parotid Gland 0.00 0.00 0.005.48 9.12 0.00 Placenta Clontech 9.17 0.00 4.59 5.26 9.51 43.58 Prostate0.00 1.35 0.68 3.00 16.67 11.25 Rectum 0.00 0.00 0.00 1.23 40.65 0.00Salivary Gland 0.00 11.84 5.92 7.31 6.84 40.49 Clontech Skeletal Muscle6.09 7.36 6.73 1.26 39.68 266.87 Clontech Skin 0.00 0.00 0.00 1.21 41.320.00 Small Intestine 0.00 0.00 0.00 0.98 51.07 0.00 Clontech Spleen 5.207.36 6.28 4.92 10.16 63.82 Stomach 12.85 6.38 9.62 2.73 18.32 176.10Testis Clontech 0.00 2.25 1.13 0.57 87.87 98.86 Thymus Clontech 177.85168.23 173.04 9.89 5.06 874.82 Thyroid 6.44 0.00 3.22 2.77 18.05 58.12Trachea Clontech 5.07 0.00 2.54 9.71 5.15 13.05 Urinary Bladder 0.000.00 0.00 5.47 9.14 0.00 Uterus 29.20 10.39 19.80 5.34 9.36 185.35copies of Reg mRNA number Mean detected/50 ng Fold Change Sample (GSKGOI total in Disease sbg471005nAChR identifier) copies RNA SamplePopulation colon normal GW98-167 21941 1530.09 3060.18 colon normalcolon tumor GW98-166 21940 617.15 1234.30 colon tumor −2.479283805 colonnormal GW98-178 22080 406.03 812.06 colon normal colon tumor GW98-17722060 1231.53 2463.06 colon tumor 3.033101002 colon normal GW98-56123514 844.37 1688.74 colon normal colon tumor GW98-560 23513 633.991267.98 colon tumor −1.331834887 colon normal GW98-894 24691 1130.512261.02 colon normal colon tumor GW98-893 24690 721.29 1442.58 colontumor −1.567344619 lung normal GW98-3 20742 2433.65 4867.30 lung normallung tumor GW98-2 20741 334.04 668.08 lung tumor −7.28550473 lung normalGW97-179 20677 823.51 1647.02 lung normal lung tumor GW97-178 20676 14922984.00 lung tumor 1.811756991 lung normal GW98-165 21922 829.65 1659.30lung normal lung tumor GW98-164 21921 595.31 1190.62 lung tumor−1.393643648 lung normal GW98-282 22584 357.69 715.38 lung normal lungtumor GW98-281 22583 256.76 513.52 lung tumor −1.393090824 breast normalGW00-392 28750 357.44 357.44 breast normal breast tumor GW00-391 28746280.98 561.96 breast tumor 1.572179946 breast normal GW00-413 28798286.18 286.18 breast normal breast tumor GW00-412 28797 195.5 391.00breast tumor 1.366272975 breast normal GW00- 27592-95 161.68 161.68breast 235:238 normal breast tumor GW00- 27588-91 217.83 217.83 breasttumor 1.347290945 231:234 breast normal GW98-621 23656 531.53 1063.06breast normal breast tumor GW98-620 23655 556.17 1112.34 breast tumor1.046356744 brain normal BB99-542 25507 143.72 287.44 brain normal brainnormal BB99-406 25509 569.17 1138.34 brain normal brain normal BB99-90425546 106.85 213.70 brain normal brain stage 5 ALZ BB99- 25502 286.37572.74 brain stage 5 1.048027423 874 ALZ brain stage 5 ALZ BB99- 25503746.74 1493.48 brain stage 5 2.732842121 887 ALZ brain stage 5 ALZ BB99-25504 382.97 765.94 brain stage 5 1.401554151 862 ALZ brain stage 5 ALZBB99- 25542 367.49 734.98 brain stage 5 1.344902042 927 ALZ CT lung KCnormal 175.41 350.82 CT lung lung 26 KC normal 20.66 20.66 lung 26 lung27 KC normal 13.06 13.06 lung 27 lung 24 KC COPD 15.89 15.89 lung 24−6.182662052 lung 28 KC COPD 7.34 7.34 lung 28 −13.38453678 lung 23 KCCOPD 22.3 22.30 lung 23 −4.405493274 lung 25 KC COPD 8.43 8.43 lung 25asthmatic lung 29321 264.47 264.47 asthmatic 2.692012113 ODO3112 lungasthmatic lung 29323 442.3 884.60 asthmatic 9.004249688 ODO3433 lungasthmatic lung 29322 670.04 1340.08 asthmatic 13.64053236 ODO3397 lungasthmatic lung 29325 414.13 828.26 asthmatic 8.430770797 ODO4928 lungendo cells KC control 66.94 66.94 endo cells endo VEGF KC 18.49 18.49endo VEGF −3.620335316 endo bFGF KC 15.93 15.93 endo bFGF −4.202134338heart Clontech normal 180.76 361.52 heart heart (T-1) ischemic 29417161.9 323.80 heart T-1 −1.116491662 heart (T-14) non- 29422 141.03282.06 heart T-14 −1.281713111 obstructive DCM heart (T-3399) DCM 29426321.32 642.64 heart T-3399 1.777605665 adenoid GW99-269 26162 193.61387.22 adenoid tonsil GW98-280 22582 625.4 1250.80 tonsil T cellsPC00314 28453 140.44 280.88 T cells PBMNC KC 0 0.00 PBMNC monocyte KC 00.00 monocyte B cells PC00665 28455 476.72 953.44 B cells dendriticcells 28441 205.79 411.58 dendritic cells neutrophils 28440 1366.991366.99 neutrophils eosinophils 28446 316.57 633.14 eosinophils BMunstim KC 29.41 29.41 BM unstim BM stim KC 46.03 46.03 BM stim1.565113907 osteo dif KC 17.47 17.47 osteo dif osteo undif KC 1.87 1.87osteo undif −9.342245989 chondrocytes 735.88 1839.70 chondrocytes OASynovium IP12/01 29462 686.8 686.80 OA Synovium OA Synovium NP10/0129461 4887.16 9774.32 OA Synovium OA Synovium NP57/00 28464 721.491442.98 OA Synovium RA Synovium NP03/01 28466 383.33 766.66 RA SynoviumRA Synovium NP71/00 28467 780.94 1561.88 RA Synovium RA Synovium NP45/0028475 543.62 1087.24 RA Synovium OA bone (biobank) 29217 780.12 780.12OA bone (biobank) OA bone Sample 1 J. Emory 361.65 723.30 OA bone OAbone Sample 2 J. Emory 197.57 395.14 OA bone Cartilage (pool) Normal220.7 441.40 Cartilage (pool) Cartilage (pool) OA 75.52 151.04 Cartilage−2.922404661 (pool) PBL unifected 28441 1745.81 3491.62 PBL unifectedPBL HIV IIIB 28442 832.4 1664.80 PBL HIV −2.097321 IIIB MRC5 uninfected29158 147.92 295.84 MRC5 (100%) uninfected (100%) MRC5 HSV strain F29178 146 292.00 MRC5 HSV −1.013150685 strain F W12 cells 29179 304.27608.54 W12 cells Keratinocytes 29180 139.44 278.88 Keratinocytes

[0146] Gene Name sbg471005nAChR Fold Change in Disease PopulationRelative to Disease tissues Normal colon tumor −2.48 colon tumor 3.03colon tumor −1.33 colon tumor −1.57 lung tumor −7.29 lung tumor 1.81lung tumor −1.39 lung tumor −1.39 breast tumor 1.57 breast tumor 1.37breast tumor 1.35 breast tumor 1.05 brain stage 5 ALZ 1.05 brain stage 5ALZ 2.73 brain stage 5 ALZ 1.40 brain stage 5 ALZ 1.34 lung 24 −6.18lung 28 −13.38 lung 23 −4.41 asthmatic lung 2.69 asthmatic lung 9.00asthmatic lung 13.64 asthmatic lung 8.43 endo VEGF −3.62 endo bFGF −4.20heart T-1 −1.12 heart T-14 −1.28 heart T-3399 1.78 BM stim 1.57 osteoundif −9.34 Cartilage (pool) −2.92 PBL HIV IIIB −2.10 MRC5 HSV strain F−1.01

[0147] Gene Name sbg442445PROa

[0148] Strong expression in B-cells with expression in other immune celltypes indicate function in immune system. Corroborating expression in RAand OA samples indicate role in disease. 2× increase in cells infectedwith HIV suggests possible marker in HIV infection. Expression in wholebrain but not cortex or cerebellum suggests localized expression inbrain. copies of mRNA detected/ Mean GOI Mean GOI Average 18S 50 ng/18S50 ng Sample copies copies GOI rRNA rRNA total sbg442445PROa (sample 1)(sample 2) Copies (ng) (ng) RNA Subcutaneous 1.13 3.82 2.48 3.06 16.3440.44 Adipocytes Zenbio Subcutaneous Adipose 0.63 0 0.32 0.96 52.3616.49 Zenbio Adrenal Gland Clontech 0.64 0.74 0.69 0.61 81.97 56.56Whole Brain Clontech 368.87 396.51 382.69 7.24 6.91 2642.89 Fetal BrainClontech 1.57 2.5 2.04 0.48 103.95 211.54 Cerebellum Clontech 1.63 00.82 2.17 23.04 18.78 Cervix 4.57 5.6 5.09 2.42 20.66 105.06 Colon 18.137.38 12.76 2.71 18.45 235.33 Endometrium 4.23 0 2.12 0.73 68.21 144.27Esophagus 6.85 12.66 9.76 1.37 36.50 356.02 Heart Clontech 12.83 1.447.14 1.32 37.88 270.27 Hypothalamus 0.58 7.26 3.92 0.32 155.28 608.70Ileum 22.89 6.34 14.62 2.58 19.38 283.24 Jejunum 6.67 36.71 21.69 6.607.58 164.32 Kidney 2.82 6.28 4.55 2.12 23.58 107.31 Liver 11.21 1.246.23 1.50 33.33 207.50 Fetal Liver Clontech 118 135.81 126.91 10.40 4.81610.12 Lung 13.95 37.87 25.91 2.57 19.46 504.09 Mammary Gland 15.7711.19 13.48 13.00 3.85 51.85 Clontech Myometriun 16.26 49.21 32.74 2.3421.37 699.47 Omeatum 16.64 25.59 21.12 3.94 12.69 267.96 Ovary 4.98 7.486.23 4.34 11.52 71.77 Pancreas 1.23 0 0.62 0.81 61.80 38.01 Head ofPancreas 3.57 0 1.79 1.57 31.85 56.85 Parotid Gland 0.59 0 0.30 5.489.12 2.69 Placenta Clontech 2.67 2.75 2.71 5.26 9.51 25.76 Prostate 9.237.92 8.58 3.00 16.67 142.92 Rectum 2.62 4.28 3.45 1.23 40.65 140.24Salivary Gland 1.02 14.59 7.81 7.31 6.84 53.39 Clontech Skeletal Muscle0 0.98 0.49 1.26 39.68 19.44 Clontech Skin 2.72 0 1.36 1.21 41.32 56.20Small Intestine 0.99 1 1.00 0.98 51.07 50.82 Clontech Spleen 31.29 42.1636.73 4.92 10.16 373.22 Stomach 15.74 7.87 2.73 18.32 144.14 TestisClontech 4.63 2.77 3.70 0.57 87.87 325.13 Thymus Clontech 503.91 615.6559.76 9.89 5.06 2829.90 Thyroid 0.75 10.38 5.57 2.77 18.05 100.45Trachea Clontech 65.95 52.98 59.47 9.71 5.15 306.20 Urinary Bladder 9.13.76 6.43 5.47 9.14 58.78 Uterus 13.88 4.35 9.12 5.34 9.36 85.35 copiesof Reg mRNA number Mean detected/50 ng Fold Change Sample (GSK GOI totalin Disease sbg442445PROa identifier) copies RNA Sample Population colonnormal GW98-167 21941 392.89 785.78 colon normal colon tumor GW98-16621940 466.75 933.50 colon tumor 1.18799155 colon normal GW98-178 22080113.54 227.08 colon normal colon tumor GW98-177 22060 43.88 87.76 colontumor −2.587511395 colon normal GW98-561 23514 335.16 670.32 colonnormal colon tumor GW98-560 23513 173.85 347.70 colon tumor −1.927868852colon normal GW98-894 24691 288.76 577.52 colon normal colon tumorGW98-893 24690 164.44 328.88 colon tumor −1.756020433 lung normal GW98-320742 2119.16 4238.32 lung normal lung tumor GW98-2 20741 33.63 67.26lung tumor −63.01397562 lung normal GW97-179 20677 1213.42 2426.84 lungnormal lung tumor GW97-178 20676 2011.79 4023.58 lung tumor 1.657950256lung normal GW98-165 21922 2088.93 4177.86 lung normal lung tumorGW98-164 21921 862.54 1725.08 lung tumor −2.421835509 lung normalGW98-282 22584 499.54 999.08 lung normal lung tumor GW98-281 22583946.36 1892.72 lung tumor 1.894462906 breast normal GW00-392 28750208.96 208.96 breast normal breast tumor GW00-391 28746 259.34 518.68breast tumor 2.48219755 breast normal GW00-413 28798 65.02 65.02 breastnormal breast tumor GW00-412 28797 493.02 986.04 breast tumor15.16517994 breast normal GW00- 27592-95 24.18 24.18 breast normal235:238 breast tumor GW00- 27588-91 126.63 126.63 breast tumor5.236972705 231:234 breast normal GW98-621 23656 536.09 1072.18 breastnormal breast tumor GW98-620 23655 203.7 407.40 breast tumor−2.631762396 brain normal BB99-542 25507 88.47 176.94 brain normal brainnormal BB99-406 25509 147.87 295.74 brain normal brain normal BB99-90425546 35.13 70.26 brain normal brain stage 5 ALZ BB99- 25502 75.02150.04 brain stage 5 −1.206211677 874 ALZ brain stage 5 ALZ BB99- 25503189 378.00 brain stage 5 2.088628578 887 ALZ brain stage 5 ALZ BB99-25504 131.38 262.76 brain stage 5 1.451873135 862 ALZ brain stage 5 ALZBB99- 25542 36.77 73.54 brain stage 5 −2.46097362 927 ALZ CT lung KCnormal 1441.16 2882.32 CT lung lung 26 KC normal 69.7 69.70 lung 26 lung27 KC normal 59.95 59.95 lung 27 lung 24 KC COPD 5.33 5.33 lung 24−142.0727017 lung 28 KC COPD 30.24 30.24 lung 28 −25.04125331 lung 23 KCCOPD 52.96 52.96 lung 23 −14.29847998 lung 25 KC COPD 17.02 17.02 lung25 asthmatic lung 29321 309.94 309.94 asthmatic −2.44320675 ODO3112 lungasthmatic lung 29323 532.32 1064.64 asthmatic 1.405933991 ODO3433 lungasthmatic lung 29322 1159.05 2318.10 asthmatic 3.061218426 ODO3397 lungasthmatic lung 29325 873.73 1747.46 asthmatic 2.307647103 ODO4928 lungendo cells KC control 0 0.00 endo cells endo VEGF KC 0.93 0.93 endo VEGF0.93 endo bFGF KC 5.16 5.16 endo bFGF 5.16 heart Clontech normal 43.0186.02 heart heart (T-1) ischemic 29417 81.55 163.10 heart T-11.896070681 heart (T-14) non- 29422 51.64 103.28 heart T-14 1.200651011obstructive DCM heart (T-3399) DCM 29426 90.27 180.54 heart T-33992.098814229 adenoid GW99-269 26162 982.05 1964.10 adenoid tonsilGW98-280 22582 3981.71 7963.42 tonsil T cells PC00314 28453 265.95531.90 T cells PBMNC KC 40.89 40.89 PBMNC monocyte KC 62.92 125.84monocyte B cells PC00665 28455 9045.58 18091.16 B cells dendritic cells28441 267.47 534.94 dendritic cells neutrophils 28440 1212.1 1212.10neutrophils eosinophils 28446 1563.76 3127.52 eosinophils BM unstim KC56.55 56.55 BM unstim BM stim KC 27.4 27.40 BM stim −2.063868613 osteodif KC 0 0.00 osteo dif osteo undif KC 0 0.00 osteo undif 0 chondrocytes0.92 2.30 chondrocytes OA Synovium IP12/01 29462 524.44 524.44 OASynovium OA Synovium NP10/01 29461 191.8 383.60 OA Synovium OA SynoviumNP57/00 28464 461.09 922.18 OA Synovium RA Synovium NP03/01 28466 484.63969.26 RA Synovium RA Synovium NP71/00 28467 698.08 1396.16 RA SynoviumRA Synovium NP45/00 28475 1034.78 2069.56 RA Synovium OA bone (biobank)29217 547.68 547.68 OA bone (biobank) OA bone Sample 1 J. Emory 286.6573.20 OA bone OA bone Sample 2 J. Emory 604.86 1209.72 OA boneCartilage (pool) Normal 224.68 449.36 Cartilage (pool) Cartilage (pool)OA 113.78 227.56 Cartilage −1.974687994 (pool) PBL unifected 28441966.68 1933.36 PBL unifected PBL HIV IIIB 28442 1353.87 2707.74 PBL HIV1.400535855 IIIB MRC5 uninfected 29158 1.28 2.56 MRC5 (100%) uninfected(100%) MRC5 HSV strain F 29178 34.07 68.14 MRC5 HSV 26.6171875 strain FW12 cells 29179 3.55 7.10 W12cells Keratinocytes 29180 5.64 11.28Keratinocytes

[0149] Gene Name sbg442445PROa Fold Change in Disease PopulationRelative to Disease tissues Normal colon tumor 1.19 colon tumor −2.59colon tumor −1.93 colon tumor −1.76 lung tumor −63.01 lung tumor 1.66lung tumor −2.42 lung tumor 1.89 breast tumor 2.48 breast tumor 15.17breast tumor 5.24 breast tumor −2.63 brain stage 5 ALZ −1.21 brain stage5 ALZ 2.09 brain stage 5 ALZ 1.45 brain stage 5 ALZ −2.46 lung 24−142.07 lung 28 −25.04 lung 23 −14.30 asthmatic lung −2.44 asthmaticlung 1.41 asthmatic lung 3.06 asthmatic lung 2.31 endo VEGF 0.93 endobFGF 5.16 heart T-1 1.90 heart T-14 1.20 heart T-3399 2.10 BM stim −2.06osteo undif 0.00 Cartilage (pool) −1.97 PBL HIV IIIB 1.40 MRC5 HSVstrain F 26.62

[0150] Gene Name sbg456548CytoRa

[0151] Strongly expressed in adenoid/tonsils and dendritic cells.Overexpressed in stimulated bone marrow. Taken together, these datasuggest a role in immune function. Expression in GI tract suggestspotential role in diseases of the GI system like IBD, Chron's, etc.copies of mRNA detected/ Mean GOI Mean GOI Average 18S 50 ng/18S 50 ngSample copies copies GOI rRNA rRNA total sbg456548CytoRa (sample 1)(sample 2) Copies (ng) (ng) RNA Subcutaneous 0.00 5.06 2.53 3.06 16.3441.34 Adipocytes Zenbio Subcutaneous Adipose 0.00 0.00 0.00 0.96 52.360.00 Zenbio Adrenal Gland Clontech 0.00 0.00 0.00 0.61 81.97 0.00 WholeBrain Clontech 0.00 0.00 0.00 7.24 6.91 0.00 Fetal Brain Clontech 0.000.00 0.00 0.48 103.95 0.00 Cerebellum Clontech 0.00 0.00 0.00 2.17 23.040.00 Cervix 0.00 7.86 3.93 2.42 20.66 81.20 Colon 9.12 37.61 23.37 2.7118.45 431.09 Endometrium 0.00 0.00 0.00 0.73 68.21 0.00 Esophagus 0.000.00 0.00 1.37 36.50 0.00 Heart Clontech 0.00 0.00 0.00 1.32 37.88 0.00Hypothalamus 0.00 0.00 0.00 0.32 155.28 0.00 Ileum not done 39.63 39.632.58 19.38 768.02 Jejunum 9.16 33.67 21.42 6.60 7.58 162.23 Kidney 0.000.00 0.00 2.12 23.58 0.00 Liver 0.00 13.75 6.88 1.50 33.33 229.17 FetalLiver Clontech 0.00 0.00 0.00 10.40 4.81 0.00 Lung 0.00 0.00 0.00 2.5719.46 0.00 Mammary Gland 136.73 106.34 121.54 13.00 3.85 467.44 ClontechMyometrium 27.33 17.56 22.45 2.34 21.37 479.59 Omentum 0.00 12.61 6.313.94 12.69 80.01 Ovary 16.46 17.90 17.18 4.34 11.52 197.93 Pancreas 0.000.00 0.00 0.81 61.80 0.00 Head of Pancreas 0.00 0.00 0.00 1.57 31.850.00 Parotid Gland 21.25 23.72 22.49 5.48 9.12 205.16 Placenta Clontech101.11 73.40 87.26 5.26 9.51 829.42 Prostate 8.55 0.00 4.28 3.00 16.6771.25 Rectum 0.00 0.00 0.00 1.23 40.65 0.00 Salivary Gland 0.00 0.000.00 7.31 6.84 0.00 Clontech Skeletal Muscle 0.00 0.00 0.00 1.26 39.680.00 Clontech Skin 0.00 0.00 0.00 1.21 41.32 0.00 Small Intestine 0.000.00 0.00 0.98 51.07 0.00 Clontech Spleen 31.60 14.66 23.13 4.92 10.16235.06 Stomach 0.00 7.01 3.51 2.73 18.32 64.19 Testis Clontech 0.00 0.000.00 0.57 87.87 0.00 Thymus Clontech 51.70 103.21 77.46 9.89 5.06 391.58Thyroid 0.00 0.00 0.00 2.77 18.05 0.00 Trachea Clontech 0.00 0.00 0.009.71 5.15 0.00 Urinary Bladder 0.00 7.29 3.65 5.47 9.14 33.32 Uterus5.98 21.02 13.50 5.34 9.36 126.40 copies of Reg mRNA number Meandetected/50 ng Fold Change in Sample (GSK GOI total Diseasesbg456548CytoRa identifier) copies RNA Sample Population colon normalGW98-167 21941 54.19 108.38 colon normal colon tumor GW98-166 21940242.87 485.74 colon tumor 4.481823215 colon normal GW98-178 22080 24.6149.22 colon normal colon tumor GW98-177 22060 17.37 34.74 colon tumor−1.416810593 colon normal GW98-561 23514 120.13 240.26 colon normalcolon tumor GW98-560 23513 43.05 86.10 colon tumor −2.79047619 colonnormal GW98-894 24691 81.35 162.70 colon normal colon tumor GW98-89324690 16.94 33.88 colon tumor −4.802243211 lung normal GW98-3 2074212.83 25.66 lung normal lung tumor GW98-2 20741 94.41 188.82 lung tumor7.358534684 lung normal GW97-179 20677 519.7 1039.40 lung normal lungtumor GW97-178 20676 46.83 93.66 lung tumor −11.09758702 lung normalGW98-165 21922 7.95 15.90 lung normal lung tumor GW98-164 21921 237.54475.08 lung tumor 29.87924528 lung normal GW98-282 22584 251.04 502.08lung normal lung tumor GW98-281 22583 28.16 56.32 lung tumor−8.914772727 breast normal GW00-392 28750 138.99 138.99 breast normalbreast tumor GW00-391 28746 147.66 295.32 breast tumor 2.124757177breast normal GW00-413 28798 30.39 30.39 breast normal breast tumorGW00-412 28797 37.64 75.28 breast tumor 2.477130635 breast normal GW00-27592-95 218.09 218.09 breast 235:238 normal breast tumor GW00- 27588-9114.68 14.68 breast tumor −14.85626703 231:234 breast normal GW98-62123656 1888.3 3776.60 breast normal breast tumor GW98-620 23655 877.21754.40 breast tumor −2.152644779 brain normal BB99-542 25507 0 0.00brain normal brain normal BB99-406 25509 0 0.00 brain normal brainnormal BB99-904 25546 0 0.00 brain normal brain stage 5 ALZ BB99- 255020 0.00 brain stage 5 0 874 ALZ brain stage 5 ALZ BB99- 25503 7.32 14.64brain stage 5 14.64 887 ALZ brain stage 5 ALZ BB99- 25504 0 0.00 brainstage 5 0 862 ALZ brain stage 5 ALZ BB99- 25542 0 0.00 brain stage 5 0927 ALZ CT lung KC normal 10.31 20.62 CT lung lung 26 KC normal 49.7949.79 lung 26 lung 27 KC normal 4.11 4.11 lung 27 lung 24 KC COPD 0.670.67 lung 24 −38.10074627 lung 28 KC COPD 19.24 19.24 lung 28−1.326793139 lung 23 KC COPD 3.15 3.15 lung 23 −8.103968254 lung 25 KCCOPD 27.59 27.59 lung 25 asthmatic lung 29321 2.95 2.95 asthmatic−8.653389831 ODO3112 lung asthmatic lung 29323 9.86 19.72 asthmatic−1.294497972 ODO3433 lung asthmatic lung 29322 24.39 48.78 asthmatic1.910880423 ODO3397 lung asthmatic lung 29325 53.84 107.68 asthmatic4.218196063 ODO4928 lung endo cells KC control 0 0.00 endo cells endoVEGF KC 14.65 14.65 endo VEGF 14.65 endo bFGF KC 0 0.00 endo bFGF 0heart Clontech normal 0 0.00 heart heart (T-1 ) ischemic 29417 21.1842.36 heart T-1 42.36 heart (T-14) non- 29422 27.4 54.80 heart T-14 54.8obstructive DCM heart (T-3399) DCM 29426 93.27 186.54 heart T-3399186.54 adenoid GW99-269 26162 579.69 1159.38 adenoid tonsil GW98-28022582 3780.08 7560.16 tonsil T cells PG00314 28453 5.86 11.72 T cellsPBMNC KC 0 0.00 PBMNC monocyte KC 0 0.00 monocyte B cells PG00665 2845519.6 39.20 B cells dendritic cells 28441 580.67 1161.34 dendritic cellsneutrophils 28440 19.76 19.76 neutrophils eosinophils 28446 15.12 30.24eosinophils BM unstim KC 0 0.00 BM unstim BM stim KC 296.72 296.72 BMstim 296.72 osteo dif KC 0 0.00 osteo dif osteo undif KC 0 0.00 osteoundif 0 chondrocytes 15.31 38.28 chondrocytes OA Synovium IP12/01 2946239.57 39.57 OA Synovium OA Synovium NP10/01 29461 0 0.00 OA Synovium OASynovium NP57/00 28464 70.08 140.16 OA Synovium RA Synovium NP03/0128466 23.73 47.46 RA Synovium RA Synovium NP71/00 28467 24.13 48.26 RASynovium RA Synovium NP45/00 28475 51.88 103.76 RA Synovium OA bone(biobank) 29217 0 0.00 OA bone (biobank) OA bone Sample 1 J. Emory 00.00 OA bone OA bone Sample 2 J. Emory 5.45 10.90 OA bone Cartilage(pool) Normal 0 0.00 Cartilage (pool) Cartilage (pool) OA 0 0.00Cartilage 0 (pool) PBL unifected 28441 76.67 153.34 PBL unifected PBLHIV IIIB 28442 13.77 27.54 PBL HIV −5.567901235 IIIB MRC5 uninfected29158 0 0.00 MRC5 (100%) uninfected (100%) MRC5 HSV strain F 29178 00.00 MRC5 HSV 0 strain F W12 cells 29179 0 0.00 W12 cells Keratinocytes29180 0 0.00 Keratinocytes

[0152] Gene Name sbg456548CytoRa Fold Change in Disease PopulationRelative to Disease tissues Normal colon tumor 4.48 colon tumor −1.42colon tumor −2.79 colon tumor −4.80 lung tumor 7.36

[0153] Gene Name sbg442358PROa

[0154] Expression in multiple immune cell types as well as stimulatedbone marrow and thymus strongly suggests function in immune system.Overexpressed in breast tumors (1/4). Expression in RA and OA withcorroborating expression in immune cells suggests role in thesediseases. Overexpressed in heart disease suggesting role in CV diseases.Downregulated in HSV infected cells suggesting possible host cellfactor. copies of mRNA detected/ Mean GOI Mean GOI Average 18S 50 ng/18S50 ng Sample copies copies GOI rRNA rRNA total sbg442358PROa (sample 1)(sample 2) Copies (ng) (ng) RNA Subcutaneous 1.86 1.71 1.79 3.06 16.3429.17 Adipocytes Zenbio Subcutaneous Adipose 0.71 0.73 0.72 0.96 52.3637.70 Zenbio Adrenal Gland Clontech 3.45 1.89 2.67 0.61 81.97 218.85Whole Brain Clontech 406.27 496.60 451.44 7.24 6.91 3117.65 Fetal BrainClontech 3.82 1.68 2.75 0.48 103.95 285.86 Cerebellum Clontech 5.8430.51 18.18 2.17 23.04 418.78 Cervix 2.50 0.48 1.49 2.42 20.66 30.79Colon 18.45 18.77 18.61 2.71 18.45 343.36 Endometrium 4.93 0.30 2.620.73 68.21 178.38 Esophagus 8.97 6.99 7.98 1.37 36.50 291.24 HeartClontech 5.26 16.53 10.90 1.32 37.88 412.69 Hypothalamus 2.10 2.41 2.260.32 155.28 350.16 Ileum 18.94 12.62 15.78 2.58 19.38 305.81 Jejunum65.51 95.24 80.38 6.60 7.58 608.90 Kidney 2.60 3.81 3.21 2.12 23.5875.59 Liver 7.19 7.05 7.12 1.50 33.33 237.33 Fetal Liver Clontech1252.22 1363.06 1307.64 10.40 4.81 6286.73 Lung 27.57 6.97 17.27 2.5719.46 335.99 Mammary Gland 79.83 72.99 76.41 13.00 3.85 293.88 ClontechMyometrium 2.46 10.62 6.54 2.34 21.37 139.74 Omentum 10.40 3.27 6.843.94 12.69 86.74 Ovary 17.71 31.15 24.43 4.34 11.52 281.45 Pancreas 3.331.74 2.54 0.81 61.80 156.67 Head of Pancreas 3.82 6.17 5.00 1.57 31.85159.08 Parotid Gland 22.77 22.54 22.66 5.48 9.12 206.71 PlacentaClontech 14.71 53.83 34.27 5.26 9.51 325.76 Prostate 16.71 19.39 18.053.00 16.67 300.83 Rectum 6.71 3.49 5.10 1.23 40.65 207.32 Salivary Gland55.38 9.30 32.34 7.31 6.84 221.20 Clontech Skeletal Muscle 3.79 4.163.98 1.26 39.68 157.74 Clontech Skin 4.51 14.47 9.49 1.21 41.32 392.15Small Intestine 8.12 7.87 8.00 0.98 51.07 408.32 Clontech Spleen 14.8817.12 16.00 4.92 10.16 162.60 Stomach 21.85 11.68 16.77 2.73 18.32307.05 Testis Clontech 22.77 11.54 17.16 0.57 87.87 1507.47 ThymusClontech 1990.82 1374.71 1682.77 9.89 5.06 8507.41 Thyroid 16.85 2.869.86 2.77 18.05 177.89 Trachea Clontech 29.69 82.85 56.27 9.71 5.15289.75 Urinary Bladder 2.32 13.42 7.87 5.47 9.14 71.94 Uterus 8.86 11.1810.02 5.34 9.36 93.82 copies of Reg mRNA number Mean detected/50 ng FoldChange Sample (GSK GOI total in Disease sbg442358PROa identifier) copiesRNA Sample Population colon normal GW98-167 21941 1232.32 2464.64 colonnormal colon tumor GW98-166 21940 2940.17 5880.34 colon tumor2.385881914 colon normal GW98-178 22080 221.26 442.52 colon normal colontumor GW98-177 22060 709.52 1419.04 colon tumor 3.20672512 colon normalGW98-561 23514 985.52 1971.04 colon normal colon tumor GW98-560 23513829.67 1659.34 colon tumor −1.18784577 colon normal GW98-894 246912738.17 5476.34 colon normal colon tumor GW98-893 24690 3022.06 6044.12colon tumor 1.103678734 lung normal GW98-3 20742 536.82 1073.64 lungnormal lung tumor GW98-2 20741 594.2 1188.40 lung tumor 1.106888715 lungnormal GW97-179 20677 4382.61 8765.22 lung normal lung tumor GW97-17820676 359.07 718.14 lung tumor −12.20544741 lung normal GW98-165 21922622.06 1244.12 lung normal lung tumor GW98-164 21921 1299.85 2599.70lung tumor 2.089589429 lung normal GW98-282 22584 1782.09 3564.18 lungnormal lung tumor GW98-281 22583 470.51 941.02 lung tumor −3.787570934breast normal GW00-392 28750 429 429.00 breast normal breast tumorGW00-391 28746 417.99 835.98 breast tumor 1.948671329 breast normalGW00-413 28798 16.03 16.03 breast normal breast tumor GW00-412 287971048.11 2096.22 breast tumor 130.768559 breast normal GW00- 27592-952.17 2.17 breast normal 235:238 breast tumor GW00- 27588-91 69.91 69.91breast tumor 32.21658986 231:234 breast normal GW98-621 23656 1037.082074.16 breast normal breast tumor GW98-620 23655 1010.59 2021.18 breasttumor −1.026212411 brain normal BB99-542 25507 299.28 598.56 brainnormal brain normal BB99-406 25509 250.85 501.70 brain normal brainnormal BB99-904 25546 97.7 195.40 brain normal brain stage 5 ALZ BB99-25502 125 250.00 brain stage 5 −1.727546667 874 ALZ brain stage 5 ALZBB99- 25503 850.01 1700.02 brain stage 5 3.936264143 887 ALZ brain stage5 ALZ BB99- 25504 347.91 695.82 brain stage 5 1.611117114 862 ALZ brainstage 5 ALZ BB99- 25542 147.11 294.22 brain stage 5 −1.467903836 927 ALZCT lung KC normal 130.37 260.74 CT lung lung 26 KC normal 159.19 159.19lung 26 lung 27 KC normal 0.49 0.49 lung 27 lung 24 KC COPD 2.37 2.37lung 24 −47.89873418 lung 28 KC COPD 45.72 45.72 lung 28 −2.482939633lung 23 KC COPD 20.36 20.36 lung 23 −5.575638507 lung 25 KC COPD 33.6633.66 lung 25 asthmatic lung 29321 65.46 65.46 asthmatic −1.734188818ODO3112 lung asthmatic lung 29323 532.42 1064.84 asthmatic 9.380197322ODO3433 lung asthmatic lung 29322 2865.67 5731.34 asthmatic 50.48749119ODO3397 lung asthmatic lung 29325 494.27 988.54 asthmatic 8.708069063ODO4928 lung endo cells KC control 62.77 62.77 endo cells endo VEGF KC22.41 22.41 endo VEGF −2.800981705 endo bFGF KC 33.16 33.16 endo bFGF−1.892943305 heart Clontech normal 74.18 148.36 heart heart ( T-1 )ischemic 29417 270.07 540.14 heart T-1 3.640738744 heart (T-14) non-29422 680.12 1360.24 heart T-14 9.168509032 obstructive DCM heart(T-3399) DCM 29426 414 828.00 heart T-3399 5.581019143 adenoid GW99-26926162 781.46 1562.92 adenoid tonsil GW98-280 22582 2279.13 4558.26tonsil T cells PC00314 28453 1129.27 2258.54 T cells PBMNC KC 27.9827.98 PBMNC monocyte KC 3.55 7.10 monocyte B cells PC00665 28455 872.581745.16 B cells dendritic cells 28441 1055.22 2110.44 dendritic cellsneutrophils 28440 740.39 740.39 neutrophils eosinophils 28446 1081.832163.66 eosinophils BM unstim KC 50.91 50.91 BM unstim BM stim KC 391.11391.11 BM stim 7.682380672 osteo dif KC 161.31 161.31 osteo dif osteoundif KC 40.01 40.01 osteo undif −4.031742064 chondrocytes 2250.595626.48 chondrocytes OA Synovium IP12/01 29462 229.19 229.19 OA SynoviumOA Synovium NP10/01 29461 152.3 304.60 OA Synovium OA Synovium NP57/0028464 413.06 826.12 OA Synovium RA Synovium NP03/01 28466 611.02 1222.04RA Synovium RA Synovium NP71/00 28467 385.94 771.88 RA Synovium RASynovium NP45/00 28475 1701.68 3403.36 RA Synovium OA bone (biobank)29217 225.69 225.69 OA bone (biobank) OA bone Sample 1 J. Emory 306.63613.26 OA bone OA bone Sample 2 J. Emory 1811.32 3622.64 OA boneCartilage (pool) Normal 384.44 768.88 Cartilage (pool) Cartilage (pool)OA 174.53 349.06 Cartilage −2.202715865 (pool) PBL unifected 284419016.82 18033.64 PBL unifected PBL HIV IIIB 28442 4331.76 8663.52 PBLHIV −2.081560382 IIIB MRC5 uninfected 29158 2232.48 4464.96 MRC5 (100%)uninfected (100%) MRC5 HSV strain F 29178 419.67 839.34 MRC5 HSV−5.319608264 strain F W12 cells 29179 3336.07 6672.14 W12 cellsKeratinocytes 29180 5568.91 11137.82 Keratinocytes

[0155] Gene Name sbg442358PROa Fold Change in Disease PopulationRelative to Disease tissues Normal colon tumor 2.39 colon tumor 3.21colon tumor −1.19 colon tumor 1.10 lung tumor 1.11 lung tumor −12.21lung tumor 2.09 lung tumor −3.79 breast tumor 1.95 breast tumor 130.77breast tumor 32.22 breast tumor −1.03 brain stage 5 ALZ −1.73 brainstage 5 ALZ 3.94 brain stage 5 ALZ 1.61 brain stage 5 ALZ −1.47 lung 24−47.90 lung 28 −2.48 lung 23 −5.58 asthmatic lung −1.73 asthmatic lung9.38 asthmatic lung 50.49 asthmatic lung 8.71 endo VEGF −2.80 endo bFGF−1.89 heart T-1 3.64 heart T-14 9.17 heart T-3399 5.58 BM stim 7.68osteo undif −4.03 Cartilage (pool) −2.20 PBL HIV IIIB −2.08 MRC5 HSVstrain F −5.32

[0156] TABLE V Additional diseases based on mRNA expression in specifictissues Tissue Expression Additional Diseases Brain Neurological andpsychiatric diseases, including Alzheimers, parasupranuclear palsey,Huntington's disease, myotonic dystrophy, anorexia, depression,schizophrenia, headache, amnesias, anxiety disorders, sleep disorders,multiple sclerosis Heart Cardiovascular diseases, including congestiveheart failure, dilated cardiomyopathy, cardiac arrhythmias, Hodgson'sDisease, myocardial infarction, cardiac arrhythmias Lung Respiratorydiseases, including asthma, Chronic Obstructive Pulmonary Disease,cystic fibrosis, acute bronchitis, adult respiratory distress syndromeLiver Dyslipidemia, hypercholesterolemia, hypertriglyceridemia,cirrhosis, hepatic encephalopatby, fatty hepatocirrhosis, viral andnonviral hepatitis, Type II Diabetes Mellitis, impaired glucosetolerance Kidney Renal diseases, including acute and chronic renalfailure, acute tubular necrosis, cystinuria, Fanconi's Syndrome,glomerulonephritis, renal cell carcinoma, renovascular hypertensionSkeletal Eulenburg's Disease, hypoglycemia, obesity, tendinitis,periodic paralyses, muscle malignant hyperthermia, paramyotoniacongenita, myotonia congenita Intestine Gastrointestinal diseases,including Myotonia congenita, Ileus, Intestinal Obstruction, TropicalSprue, Pseudomembranous Enterocolitis Spleen/lymph Lymphangiectasia,hypersplenism, angiomas, ankylosing spondylitis, Hodgkin's Disease,macroglobulinemia, malignant lymphomas, rheumatoid arthritis PlacentaChoriocarcinoma, hydatidiform mole, placenta previa Testis Testicularcancer, male reproductive diseases, including low testosterone and maleinfertility Pancreas Diabetic ketoacidosis, Type 1 & 2 diabetes,obesity, impaired glucose tolerance

[0157]

1 44 1 1383 DNA Homo sapiens 1 atgcttggaa tttggattgt tgcattcttgttctttggca catcaagagg aaaagaagtt 60 tgctatgaaa ggttagggtg tttcaaagatggtttaccat ggaccaggac tttctcaaca 120 gagttggtag gtttaccctg gtctccagagaagataaaca ctcgtttcct gctctacact 180 atacacaatc ccaatgccta tcaggagatcagtgcggtta attcttcaac tatccaagcc 240 tcatattttg gaacagacaa gatcacccgtatcaacatag ctggatggaa aacagatggc 300 aaatggcaga gagacatgtg caatgtgttgctacagctgg aagatataaa ttgcattaat 360 ttagattgga tcaacggttc acgggaatacatccatgctg taaacaatct ccgtgttgtt 420 ggtgctgagg tggcttattt tattgatgttctcatgaaaa aatttgaata ttccccttct 480 aaagtgcact tgattggcca cagcttgggagcacacctgg ctggggaagc tgggtcaagg 540 ataccaggcc ttggaagaat aactgggttggacccagctg ggccattttt ccacaacact 600 ccaaaggaag tcaggctaga cccctcggatgccaactttg ttgacgttat tcatacaaat 660 gcagctcgca tcctctttga gcttggtgttggaaccattg atgcttgtgg tcatcttgac 720 ttttacccaa atggagggaa gcacatgccaggatgtgaag acttaattac acctttactg 780 aaatttaact tcaatgctta caaaaaagaaatggcttcct tctttgactg taaccatgcc 840 cgaagttatc aattttatgc tgaaagcattcttaatcctg atgcatttat tgcttatcct 900 tgtagatcct acacatcttt taaagcaggtacatgtgtag gatgtgcaga tttgttacat 960 aggatagata agataggaag tcatacttcccatgtgtttt taaccctttc tctccctttc 1020 cttcttgttt ccttatatct aggttggaggcacaaattgt ctgttaaact cagtggaagc 1080 gaagtcactc aaggaactgt ctttcttcgtgtaggcgggg cagttaggaa aactggggag 1140 tttgccattg tcagtggaaa acttgagccaggcatgactt acacaaaatt aatcgatgca 1200 gatgttaacg ttggaaacat tacaagtgttcagttcatct ggaaaaaaca tttgtttgaa 1260 gattctcaga ataagttggg agcagaaatggtgataaata catctgggaa atatggatat 1320 aaatctacct tctgtagcca agacattatgggacctaata ttctccagaa cctgaaacca 1380 tgc 1383 2 927 DNA Homo sapiens 2atgccgttcc tgcagctgaa agggagagca acacctccat cctggagaca cgatagccgc 60tcacttgttc acctgctgga cggcaaggag ggcgtgtggg acaccacggg ctatgcctta 120gggagcagag aatcattgaa tcctgacatg gggattggtg acccacatgg acacagcact 180gtccacacca gggaagcagg cactgcctgt ccattacagc ttctaggtgc tcgggaggcc 240agtctgctgg cctgtgggat ctgccaggcc tctggccaaa tcttcatcac ccaaaccctg 300gggatcaagg gatatcggac tgtcgtggcc ctggataagg tccctgagga tgttcaggaa 360tacagctggt actggggtgc aaacgacagc gcaggaaaca tgattatcag ccacaaaccg 420cccagtgccc agcagcctgg gcccatgtac actggcaggg agagagtgaa cagagaaggc 480agcctgttga tcaggccgac tgcattaaat gacacgggaa actacactgt tcgggtggtt 540gcaggcaatg agacccaaag agcaaccggc tggctggagg ttctagatgg gcccgactat 600gtgctgctga ggagcaatcc tgatgatttc aacggcattg tgacagctga gatcggctcc 660caagtggaaa tggagtgtat ctgctattcc ttcctggatc tcaagtacca ctggatccac 720aatggctccc tcctgaactt ctcagatgca aagatgaacc tctcgagtct tgcctgggag 780cagatgggcc gttaccgatg cactgtggag aaccccgtga cacagctgat catgtacatg 840gacgtcagga tccaggcccc ccatgagtgc agcagctccc ctccaggctc atgctttgca 900catctccctg cctccatgcc ctgctag 927 3 1374 DNA Homo sapiens 3 atggacctttccagacccag atggagcctg tggaggaggg tcttcctcat ggccagtctg 60 ctggcctgtgggatctgcca ggcctctggc caaatcttca tcacccaaac cctggggatc 120 aagggatatcggactgtcgt ggccctggat aaggtccctg aggatgttca ggaatacagc 180 tggtactggggtgcaaacga cagcgcagga aacatgatta tcagccacaa accgcccagt 240 gcccagcagcctgggcccat gtacactggc agggagagag tgaacagaga aggcagcctg 300 ttgatcaggccgactgcatt aaatgacacg ggaaactaca ctgttcgggt ggttgcaggc 360 aatgagacccaaagagcaac cggctggctg gaggttctag agttgggaag caatctgggc 420 atctccgtcaatgccagctc cctggtggag aacatggatt ctgtggctgc tgactgcctc 480 acaaatgtcaccaacatcac gtggtatgtg aatgatgtgc ctacctctag tagtgaccgg 540 atgacaatttccccagacgg caagaccctc gtcatcctca gggtcagccg ctatgacaga 600 acaattcagtgcatgataga gagtttccca gagatctttc agagaagtga acgcatctct 660 ctgactgtggcctatgggcc cgactatgtg ctgctgagga gcaatcctga tgatttcaac 720 ggcattgtgacagctgagat cggctcccaa gtggaaatgg agtgtatctg ctattccttc 780 ctggatctcaagtaccactg gatccacaat ggctccctcc tgaacttctc agatgcaaag 840 atgaacctctcgagtcttgc ctgggagcag atgggccgtt accgatgcac tgtggagaac 900 cccgtgacacagctgatcat gtacatggac gtcaggatcc aggcccccca tgagtgtcct 960 cttccttcagggatcttacc tgttgtccac agagatttct ccatctcagg atccatggtg 1020 atgttcctcatcatgctgac agtgctgggt ggcgtttaca tctgtggagt cctgatccat 1080 gctctgatcaaccactactc aatcaggtgc cctcattgct ctgggacaag ggtgggatgt 1140 tggctgggggctgggactca ggagccagcc ctccctccag aggggaagca gagccagaag 1200 gggagggataagccaggaac taggttgtca gggatcatct ggggcagaca gatcagcccc 1260 caggacctgaagctgatggg agcaagagag ggtttagagt cggccatggt tctaaatagc 1320 tgtggggtttcttctagcaa cttcccttct ctttgtgttt ataagggata ttaa 1374 4 2115 DNA Homosapiens 4 atgctccatg atgggttgac tgcacctgat gggtgtggaa tctacagcctgaccgggcgg 60 gaagtcctga cgcccttccc aggattgggc actgcggcag ccccggcacagggcggggcc 120 cacctgaagc agtgtgacct gctgaagctg tcccggcggc agaagcagctctgccggagg 180 gagcccggcc tggctgagac cctgagggat gctgcgcacc tcggcctgcttgagtgccag 240 tttcagttcc ggcatgagcg ctggaactgt agcctggagg gcaggatgggcctgctcaag 300 agaggcttca aagagacagc tttcctgtac gcggtgtcct ctgccgccctcacccacacc 360 ctggcccggg cctgcagcgc tgggcgcatg gagcgctgca cctgtgatgactctccgggg 420 ctggagagcc ggcaggcctg gcagtggggc gtgtgcggtg acaacctcaagtacagcacc 480 aagtttctga gcaacttcct ggggtccaag agaggaaaca aggacctgcgggcacgggca 540 gacgcccaca atacccacgt gggcatcaag gctgtgaaga gtggcctcaggaccacgtgt 600 aagtgccatg gcgtatcagg ctcctgtgcc gtgcgcacct gctggaagcagctctccccg 660 ttccgtgaga cgggccaggt gctgaaactg cgctatgact cggctgtcaaggtgtccagt 720 gccaccaatg aggccttggg ccgcctagag ctgtgggccc ctgccaggcagggcagcctc 780 accaaaggcc tggccccaag gtctggggac ctggtgtaca tggaggactcacccagcttc 840 tgccggccca gcaagtactc acctggcaca gcaggtaggg tgtgctcccgggaggccagc 900 tgcagcagcc tgtgctgcgg gcggggctat gacacccaga gccgcctggtggccttctcc 960 tgccactgcc aggtgcagtg gtgctgctac gtggagtgcc agcaatgtgtgcaggaggag 1020 cttgtgtaca cctgcaagca ctagatgggc cctgtggggt tcccgaggcagtgccaggga 1080 gccttctttg agagcagccc tgggcagacc agggcccgcc tgaccgggcgggaagtcctg 1140 acgcccttcc caggattggg cactgcggca gccccggcac agggcggggcccacctgaag 1200 cagtgtgacc tgctgaagct gtcccggcgg cagaagcagc tctgccggagggagcccggc 1260 ctggctgaga ccctgaggga tgctgcgcac ctcggcctgc ttgagtgccagtttcagttc 1320 cggcatgagc gctggaactg tagcctggag ggcaggatgg gcctgctcaagagaggcttc 1380 aaagagacag ctttcctgta cgcggtgtcc tctgccgccc tcacccacaccctggcccgg 1440 gcctgcagcg ctgggcgcat ggagcgctgc acctgtgatg actctccggggctggagagc 1500 cggcaggcct ggcagtgggg cgtgtgcggt gacaacctca agtacagcaccaagtttctg 1560 agcaacttcc tggggtccaa gagaggaaac aaggacctgc gggcacgggcagacgcccac 1620 aatacccacg tgggcatcaa ggctgtgaag agtggcctca ggaccacgtgtaagtgccat 1680 ggcgtatcag gctcctgtgc cgtgcgcacc tgctggaagc agctctccccgttccgtgag 1740 acgggccagg tgctgaaact gcgctatgac tcggctgtca aggtgtccagtgccaccaat 1800 gaggccttgg gccgcctaga gctgtgggcc cctgccaggc agggcagcctcaccaaaggc 1860 ctggccccaa ggtctgggga cctggtgtac atggaggact cacccagcttctgccggccc 1920 agcaagtact cacctggcac agcaggtagg gtgtgctccc gggaggccagctgcagcagc 1980 ctgtgctgcg ggcggggcta tgacacccag agccgcctgg tggccttctcctgccactgc 2040 caggtgcagt ggtgctgcta cgtggagtgc cagcaatgtg tgcaggaggagcttgtgtac 2100 acctgcaagc actag 2115 5 1086 DNA Homo sapiens 5atgaagcccc tgaggaggcc ccttcccttc atttgcccct caccaccatc cccaaggctc 60acctgtctcc ctcctctcgc tctctctagc ctgaccgggc gggaagtcct gacgcccttc 120ccaggattgg gcactgcggc agccccggca cagggcgggg cccacctgaa gcagtgtgac 180ctgctgaagc tgtcccggcg gcagaagcag ctctgccgga gggagcccgg cctggctgag 240accctgaggg atgctgcgca cctcggcctg cttgagtgcc agtttcagtt ccggcatgag 300cgctggaact gtagcctgga gggcaggatg ggcctgctca agagaggctt caaagagaca 360gctttcctgt acgcggtgtc ctctgccgcc ctcacccaca ccctggcccg ggcctgcagc 420gctgggcgca tggagcgctg cacctgtgat gactctccgg ggctggagag ccggcaggcc 480tggcagtggg gcgtgtgcgg tgacaacctc aagtacagca ccaagtttct gagcaacttc 540ctggggtcca agagaggaaa caaggacctg cgggcacggg cagacgccca caatacccac 600gtgggcatca aggctgtgaa gagtggcctc aggaccacgt gtaagtgcca tggcgtatca 660ggctcctgtg ccgtgcgcac ctgctggaag cagctctccc cgttccgtga gacgggccag 720gtgctgaaac tgcgctatga ctcggctgtc aaggtgtcca gtgccaccaa tgaggccttg 780ggccgcctag agctgtgggc ccctgccagg cagggcagcc tcaccaaagg cctggcccca 840aggtctgggg acctggtgta catggaggac tcacccagct tctgccggcc cagcaagtac 900tcacctggca cagcaggtag ggtgtgctcc cgggaggcca gctgcagcag cctgtgctgc 960gggcggggct atgacaccca gagccgcctg gtggccttct cctgccactg ccaggtgcag 1020tggtgctgct acgtggagtg ccagcaatgt gtgcaggagg agcttgtgta cacctgcaag 1080cactag 1086 6 1098 DNA Homo sapiens 6 atgtggctgc ttttaacaac aacttgtttgatctgtggaa ctttaaatgc tggtggattc 60 cttgatttgg aaaatgaagt gaatcctgaggtgtggatga atactagtga aatcatcatc 120 tacaatggct accccagtga agagtatgaagtcaccactg aagatgggta tatactcctt 180 gtcaacagaa ttccttatgg gcgaacacatgctaggagca cagcagatgc aggttatgat 240 gtatggatgg gaaacagtcg gggaaacacttggtcaagaa gacacaaaac actctcagag 300 acagatgaga aattctgggc ctttagttttgatgaaatgg ccaaatatga tctcccagga 360 gtaatagact tcattgtaaa taaaactggtcaggagaaat tgtatttcat tggacattca 420 cttggcacta caatagggtt tgtagccttttccaccatgc ctgaactggc acaaagaatc 480 aaaatgaatt ttgccttggg tcctacgatctcattcaaat atcccacggg catttttacc 540 aggttttttc tacttccaaa ttccataatcaaggctgttt ttggtaccaa aggtttcttt 600 ttagaagata agaaaacgaa gatagcttctaccaaaatct gcaacaataa gatactctgg 660 ttgatatgta gcgaatttat gtccttatgggctggatcca acaagaaaaa tatgaatcag 720 agtcgaatgg atgtgtatat gtcacatgctcccactggtt catcagtaca caacattctg 780 catataaaac agctttacca ctctgatgaattcagagctt atgactgggg aaatgacgct 840 gataatatga aacattacaa tcagagtcatccccctatat atgacctgac tgccatgaaa 900 gtgcctactg ctatttgggc tggtggacatgatgtcctcg taacacccca ggatgtggcc 960 aggatactcc ctcaaatcaa gagtcttcattactttaagc tattgccaga ttggaaccac 1020 tttgattttg tctggggcct cgatgcccctcaacggatgt acagtgaaat catagcttta 1080 atgaaggcat attcctaa 1098 7 1194DNA Homo sapiens 7 atgtggcagc ttttagcagc agcatgctgg atgcttcttcttggatctat gtatggttat 60 gacaagaaag gaaacaatgc aaaccctgaa gctaatatgaatattagcca gattatttct 120 tactggggtt atccttatga agagtatgat gttacaacaaaagatggtta tatccttgga 180 atttatagga ttccacatgg aagaggatgc ccagggaggacagctccaaa gcctgctgtg 240 tatttgcagc atggcttaat tgcatctgcc agtaactggatttgcaacct gcccaacaac 300 agtttggctt tccttctggc agatagtggt tatgacgtgtggttggggaa cagccgagga 360 aacacttggt ccagaaaaca ccttaaattg tcaccgaaatcaccggaata ctgggccttc 420 agtttggatg agatggctaa atatgacctt ccagccacaatcaattttat catagagaaa 480 actggacaga agcgactcta ctacgtgggc cactcacaaggcaccaccat agcttttata 540 gcattttcta caaacccaga actggctaaa aagattaagatattttttgc actggctcca 600 gttgtcacag ttaaatacac ccaaagtcct atgaaaaaactaacaaccct ttccaggcga 660 gtagttaagg tgttgtttgg tgacaaaatg ttccaccctcatacattgtt tgaccaattc 720 attgccacca aagtgtgcaa tcgaaagcta ttccgtcgtatttgcagcaa cttcctattt 780 actctgagtg gatttgatcc gcaaaactta aatatgagtcgcttggatgt ttatttgtca 840 cacaatcctg cgggaacatc tgttcagaat atgctgcactgggctcagct ttaccactct 900 gatgaattca gagcttatga ctggggaaat gacgctgataatatgaaaca ttacaatcag 960 agtcatcccc ctatatatga cctgactgcc atgaaagtgcctactgctat ttgggctggt 1020 ggacatgatg tcctcgtaac accccaggat gtggccaggatactccctca aatcaagagt 1080 cttcattact ttaagctatt gccagattgg aaccactttgattttgtctg gggcctcgat 1140 gcccctcaac ggatgtacag tgaaatcata gctttaatgaaggcatattc ctaa 1194 8 11118 DNA Homo sapiens 8 atggcgaagc ggctctgcgcggggagcgca ctgtgtgttc gcggcccccg gggccccgcg 60 ccgctgctgc tggtcgggctggcgctgctg ggcgcggcgc gggcgcggga ggaggcgggc 120 ggcggcttca gcctgcacccgccctacttc aacctggccg agggcgcccg catcgccgcc 180 tccgcgacct gcggagaggaggccccggcg cgcggctccc cgcgccccac cgaggacctt 240 tactgcaagc tggtagggggccccgtggcc ggcggcgacc ccaaccagac catccggggc 300 cagtactgtg acatctgcacggctgccaac agcaacaagg cacaccccgc gagcaatgcc 360 atcgatggca cggagcgctggtggcagagt ccaccgctgt cccgcggcct ggagtacaac 420 gaggtcaacg tcaccctggacctgggccag gtcttccacg tggcctacgt cctcatcaag 480 tttgccaact caccccggccggacctctgg gtgctggagc ggtccatgga cttcggccgc 540 acctaccagc cctggcagttctttgcctcc tccaagaggg actgtctgga gcggttcggg 600 ccacagacgc tggagcgcatcacacgggac gacgcggcca tctgcaccac cgagtactca 660 cgcatcgtgc ccctggagaacggagagatc gtggtgtccc tggtgaacgg acgtccgggc 720 gccatgaatt tctcctactcgccgctgcta cgtgagttca ccaaggccac caacgtccgc 780 ctgcgcttcc tgcgtaccaacacgctgctg ggccatctca tggggaaggc gctgcgggac 840 cccacggtca cccgccggtattattacagc atcaaggata tcagcatcgg aggccgctgt 900 gtctgccacg gccacgcggatgcctgcgat gccaaagacc ccacggaccc gttcaggctg 960 cagtgcacct gccagcacaacacctgcggg ggcacctgcg accgctgctg ccccggcttc 1020 aatcagcagc cgtggaagcctgcgactgcc aacagtgcca acgagtgcca gtcctgtaac 1080 tgctacggcc atgccaccgactgttactac gaccctgagg tggaccggcg ccgcgccagc 1140 cagagcctgg atggcacctatcagggtggg ggtgtctgta tcgactgcca gcaccacacc 1200 accggcgtca actgtgagcgctgcctgccc ggcttctacc gctctcccaa ccaccctctc 1260 gactcgcccc acgtctgccgccgctgcaac tgcgagtccg acttcacgga tggcacctgc 1320 gaggacctga cgggtcgatgctactgccgg cccaacttct ctggggagcg gtgtgacgtg 1380 tgtgccgagg gcttcacgggcttcccaagc tgctacccga cgccctcgtc ctccaatgac 1440 accagggagc aggtgctgccagccggccag attgtgaatt gtgactgcag cgcggcaggg 1500 acccagggca acgcctgccggaaggaccca agggtgggac gctgtctgtg caaacccaac 1560 ttccaaggca cccattgtgagctctgcgcg ccagggttct acggccccgg ctgccagccc 1620 tgccagtgtt ccagccctggagtggccgat gaccgctgtg accctgacac aggccagtgc 1680 aggtgccgag tgggcttcgagggggccaca tgtgatcgct gtgcccccgg ctactttcac 1740 ttccctctct gccagttgtgtggctgcagc cctgcaggaa ccttgcccga gggctgcgat 1800 gaggccggcc gctgcctatgccagcctgag tttgctggac ctcattgtga ccggtgccgc 1860 cctggctacc atggtttccccaactgccaa gcatgcacct gcgaccctcg gggagccctg 1920 gaccagctct gtggggcgggaggtttgtgc cgctgccgcc ccggctacac aggcactgcc 1980 tgccaggaat gcagccccggctttcacggc ttccccagct gtgtcccctg ccactgctct 2040 gctgaaggct ccctgcacgcagcctgtgac ccccggagtg ggcagtgcag ctgccggccc 2100 cgtgtgacgg ggctgcggtgtgacacatgt gtgcccggtg cctacaactt cccctactgc 2160 gaagctggct cttgccaccctgccggtctg gccccagtgg atcctgccct tcctgaggca 2220 caggttccct gtatgtgccgggctcacgtg gaggggccga gctgtgaccg ctgcaaacct 2280 gggttctggg gactgagccccagcaacccc gagggctgta cccgctgcag ctgcgacctc 2340 aggggcacac tgggtggagttgctgagtgc cagccgggca ccggccagtg cttctgcaag 2400 ccccacgtgt gcggccaggcctgcgcgtcc tgcaaggatg gcttctttgg actggatcag 2460 gctgactatt ttggctgccgcagctgccgg tgtgacattg gcggtgcact gggccagagc 2520 tgtgaaccga ggacgggcgtctgccggtgc cgccccaaca cccagggccc cacctgcagc 2580 gagcctgcga gggaccactacctcccggac ctgcaccacc tgcgcctgga gctggaggag 2640 gctgccacac ctgagggtcacgccgtgcgc tttggcttca accccctcga gttcgagaac 2700 ttcagctgga ggggctacgcgcagatggca cctgtccagc ccaggatcgt ggccaggctg 2760 aacctgacct cccctgaccttttctggctc gtcttccgat acgtcaaccg gggggccatg 2820 agtgtgagcg ggcgggtctctgtgcgagag gagggcaggt cggccacctg cgccaactgc 2880 acagcacaga gtcagcccgtggccttccca cccagcacgg agcctgcctt catcaccgtg 2940 ccccagaggg gcttcggagagccctttgtg ctgaaccctg gcacctgggc cctgcgtgtg 3000 gaggccgaag gggtgctcctggactacgtg gttctgctgc ctagcgcata ctacgaggcg 3060 gcgctcctgc agctgcgggtgactgaggcc tgcacatacc gtccctctgc ccagcagtct 3120 ggcgacaact gcctcctctacacacacctc cccctggatg gcttcccctc ggccgccggg 3180 ctggaggccc tgtgtcgccaggacaacagc ctgccccggc cctgccccac ggagcagctc 3240 agcccgtcgc acccgccactgatcacctgc acgggcagtg atgtggacgt ccagcttcaa 3300 gtggcagtgc cacagccaggccgctatgcc ctagtggtgg agtacgccaa tgaggatgcc 3360 cgccaggagg tgggcgtggccgtgcacacc ccacagcggg ccccccagca ggggctgctc 3420 tccctgcacc cctgcctgtacagcaccctg tgccggggca ctgcccggga tacccaggac 3480 cacctggctg tcttccacctggactcggag gccagcgtga ggctcacagc cgaacaggca 3540 cgcttcttcc tgcacggggtcactctggtg cccattgagg agttcagccc ggagttcgtg 3600 gagccccggg tcagctgcatcagcagccac ggcgcctttg gccccaacag tgccgcctgt 3660 ctgccctcgc gcttcccaaagccgccccag cccatcatcc tcagggactg ccaggtgatc 3720 ccgctgccgc ccggcctcccgctgacccac gcgcaggatc tcactccagc catgtcccca 3780 gctggacccc gacctcggccccccaccgct gtggaccctg atgcagagcc caccctgctg 3840 cgtgagcccc aggccaccgtggtcttcacc acccatgtgc ccacgctggg ccgctatgcc 3900 ttcctgctgc acggctaccagccagcccac cccaccttcc ccgtggaagt cctcatcaac 3960 gccggccgcg tgtggcagggccacgccaac gccagcttct gtccacatgg ctacggctgc 4020 cgcaccctgg tggtgtgtgagggccaggcc ctgctggacg tgacccacag cgagctcact 4080 gtgaccgtgc gtgtgcccaagggccggtgg ctctggctgg attatgtact cgtggtccct 4140 gagaacgtct acagctttggctacctccgg gaggagcccc tggataaatc ctatgacttc 4200 atcagccact gcgcagcccagggctaccac atcagcccca gcagctcatc cctgttctgc 4260 cgaaacgctg ctgcttccctctccctcttc tataacaacg gagcccgtcc atgtggctgc 4320 cacgaagtag gtgctacaggccccacgtgt gagcccttcg ggggccagtg tccctgccat 4380 gcccatgtca ttggccgtgactgctcccgc tgtgccaccg gatactgggg cttccccaac 4440 tgcaggccct gtgactgcggtgcccgcctc tgtgacgagc tcacgggcca gtgcatctgc 4500 ccgccacgca ccatcccgcccgactgcctg ctgtgccagc cccagacctt tggctgccac 4560 cccctggtcg gctgtgaggagtgtaactgc tcagggcccg gcatccagga gctcacagac 4620 cctacctgtg acacagacagcggccagtgc aagtgcagac ccaacgtgac tgggcgccgc 4680 tgtgatacct gctctccgggcttccatggc tacccccgct gccgcccctg tgactgtcac 4740 gaggcgggca ctgcgcctggcgtgtgtgac cccctcacag ggcagtgcta ctgtaaggag 4800 aacgtgcagg gccccaaatgtgaccagtgc agccttggga ccttctcact ggatgctgcc 4860 aaccccaaag gttgcacccgctgcttctgc tttggggcca cggagcgctg ccggagctcg 4920 tcctacaccc gccaggagttcgtggatatg gagggatggg tgctgctgag cactgaccgg 4980 caggtggtgc cccacgagcggcagccaggg acggagatgc tccgtgcaga cctgcggcac 5040 gtgcctgagg ctgtgcccgaggctttcccc gagctgtact ggcaggcccc accctcctac 5100 ctgggggacc gggtgtcatcctacggtggg accctccgtt atgaactgca ctcagagacc 5160 cagcggggag atgtctttgtccccatggag agcaggccgg atgtggtgct gcagggcaac 5220 cagatgagca tcacattcctggagccggca taccccacgc ctggccacgt tcaccgtggg 5280 cagctgcagc tggtggaggggaacttccgg catacggaga cgcgcaacac tgtgtcccgc 5340 gaggagctca tgatggtgctggccagcctg gagcagctgc agatccgtgc cctcttctca 5400 cagatctcct cggctgtcttcctgcgcagg gtggcactgg aggtggccag cccagcaggc 5460 cagggggccc tggccagcaatgtggagctg tgcctgtgcc ccgccagcta ccggggggac 5520 tcatgccagg aatgtgcccccggcttctat cgggacgtca aaggtctctt cctgggccga 5580 tgtgtccctt gtcagtgccatggacactca gaccgctgcc tccctggctc tggcgtctgt 5640 gtggactgcc agcacaacaccgaaggggcc cactgtgagc gctgccaggc tggcttcgtg 5700 agcagcaggg acgaccccagcgccccctgt gtcagctgcc cctgccccct ctcagtgcct 5760 tccaacaact tcgccgagggctgtgtcctg cgaggcggcc gcacccagtg cctctgcaaa 5820 cctggttatg caggtgcctcctgcgagcgg tgtgcgcccg gattctttgg gaacccactg 5880 gtgctgggca gctcctgccagccatgcgac tgcagcggca acggtgaccc caacttgctc 5940 ttcagcgact gcgaccccctgacgggcgcc tgccgtggct gcctgcgcca caccactggg 6000 ccccgctgcg agatctgtgcccccggcttc tacggcaacg ccctgctgcc cggcaactgc 6060 acccggtgcg actgtaccccatgtgggaca gaggcctgcg acccccacag cgggcactgc 6120 ctgtgcaagg cgggcgtgactgggcggcgc tgtgaccgct gccaggaggg acattttggt 6180 ttcgatggct gcgggggctgccgcccgtgt gcttgtggac cggccgccga gggctccgag 6240 tgccaccccc agagcggacagtgccactgc cgaccaggga ccatgggacc ccagtgccgc 6300 gagtgtgccc ctggctactgggggctccct gagcagggct gcaggcgctg ccagtgccct 6360 gggggccgct gtgaccctcacacgggccgc tgcaactgcc ccccggggct cagcggggag 6420 cgctgcgaca cctgcagccagcagcatcag gtgcctgttc caggcgggcc tgtgggccac 6480 agcatccact gtgaagtgtgtgaccactgt gtggtcctgc tcctggatga cctggaacgg 6540 gccggcgccc tcctccccgccattcacgag caactgcgtg gcatcaatgc cagctccatg 6600 gcctgggccc gtctgcacaggctgaacgcc tccatcgctg acctgcagag ccagctccgg 6660 agccccctgg gcccccgccatgagacggca cagcagctgg aggtgctgga gcagcagagc 6720 acaagcctcg ggcaggacgcacggcggcta ggcggccagg caggagcccc aagacccccc 6780 agggccccgg gaggctttcacctgtaccag gcgagccaat tgctggccgg caccgaggcc 6840 acactgggcc atgcgaagacgctgttggcg gccatccggg ctgtggaccg caccctgagc 6900 gagctcatgt cccagacgggccacctgggg ctggccaatg cctcggctcc atcaggtgag 6960 cagctgctcc ggacactggccgaggtggag cggctgctct gggagatgcg ggcccgggac 7020 ctgggggccc cgcaggcagcagctgaggct gagttggctg cagcacagag attgctggcc 7080 cgggtgcagg agcagctgagcagcctctgg gaggagaacc aggcactggc cacacaaacc 7140 cgcgaccggc tggcccagcacgaggccggc ctcatggacc tgcgagaggc tttgaaccgg 7200 gcagtggacg ccacacgggaggcccaggag ctcaacagcc gcaaccagga gcgcctggag 7260 gaagccctgc aaaggaagcaggagctgtcc cgggacaatg ccaccctgca ggccactctg 7320 catgcggcta gggacaccctggccagcgtc ttcagattgc tgcacagcct ggaccaggct 7380 aaggaggagc tggagcgcctcgccgccagc ctggatgggg ctcggacccc actgctgcag 7440 aggatgcaga ccttctccccggcgggcagc aagctgcgtc tagtggaggc cgccgaggcc 7500 cacgcacagc agctgggccagctggcactc aatctgtcca gcatcatcct ggacgtcaac 7560 caggaccgcc tcacccagagggccatcgag gcctccaacg cctacagccg catcctgcag 7620 gccgtgcagg ctgccgaggatgctgctggc caggccctgc agcaggcgga ccacacgtgg 7680 gcgacggtgg tgcggcagggcctggtggac cgagcccagc agctcctggc caacagcact 7740 gcactagaag aggccatgctccaggaacag cagaggctgg gccttgtgtg ggctgccctc 7800 cagggtgcca ggacccagctccgagatgtc cgggccaaga aggaccagct ggaggcgcac 7860 atccaggcgg cgcaggccatgcttgccatg gacacagacg agacaagcaa gaagatcgca 7920 catgccaagg ctgtggctgctgaagcccag gacaccgcca cccgtgtgca gtcccagctg 7980 caggccatgc aggagaatgtggagcggtgg cagggccagt acgagggcct gcggggccag 8040 gacctgggcc aggcagtgcttgacgcaggc cactcagtgt ccaccctgga gaagacgctg 8100 ccccagctgc tggccaagctgagcatcctg gagaaccgtg gggtgcacaa cgccagcctg 8160 gccctgtccg ccagcattggccgcgtgcga gagctcattg cccaggcccg gggggctgcc 8220 agtaaggtca aggtgcccatgaagttcaac gggcgctcag gggtgcagct gcgcacccca 8280 cgggatcttg ccgaccttgctgcctacact gccctcaagt tctacctgca gggcccagag 8340 cctgagcctg ggcagggtaccgaggatcgc tttgtgatgt acatgggcag ccgccaggcc 8400 actggggact acatgggtgtgtctctgcgt gacaagaagg tgcactgggt gtatcagctg 8460 ggtgaggcgg gccctgcagtcctaagcatc gatgaggaca ttggggagca gttcgcagct 8520 gtcagcctgg acaggactctccagtttggc cacatgtccg tcacagtgga gagacagatg 8580 atccaggaaa ccaagggtgacacggtggcc cctggggcag aggggctgct caacctgcgg 8640 ccagacgact tcgtcttctacgtcgggggg taccccagta ccttcacgcc ccctcccctg 8700 cttcgcttcc ccggctaccggggctgcatc gagatggaca cgctgaatga ggaggtggtc 8760 agcctctaca acttcgagaggaccttccag ctggacacgg ctgtggacag gccttgtgcc 8820 cgctccaagt cgaccggggacccgtggctc acggacggct cctacctgga cggcaccggc 8880 ttcgcccgca tcagcttcgacagtcagatc agcaccacca agcgcttcga gcaggagctg 8940 cggctcgtgt cctacagcggggtgctcttc ttcctgaagc agcagagcca gttcctgtgc 9000 ttggccgtgc aagaaggcagcctcgtgctg ttgtatgact ttggggctgg cctgaaaaag 9060 gccgtcccac tgcagcccccaccgcccctg acctcggcca gcaaggcgat ccaggtgttc 9120 ctgctggggg gcagccgcaagcgtgtgctg gtgcgtgtgg agcgggccac ggtgtacagc 9180 gtggagcagg acaatgatctggagctggcc gacgcctact acctgggggg cgtgccgccc 9240 gaccagctgc ccccgagcctgcgacggctc ttccccaccg gaggctcagt ccgtggctgc 9300 gtcaaaggca tcaaggccctgggcaagtat gtggacctca agcggctgaa cacgacaggc 9360 gtgagcgccg gctgcaccgccgacctgctg gtggggcgcg ccatgacttt ccatggccac 9420 ggcttccttc gcctggcgctctcgaacgtg gcaccgctca ctggcaacgt ctactccggc 9480 ttcggcttcc acagcgcccaggacagtgcc ctgctctact accgggcgtc cccggatggg 9540 ctatgccagg tgtccctgcagcagggccgt gtgagcctac agctcctgag gactgaagtg 9600 aaaactcaag cgggcttcgccgatggtgcc ccccattacg tcgccttcta cagcaatgcc 9660 acgggagtct ggctgtatgtcgatgaccag ctccagcaga tgaagcccca ccggggacca 9720 ccccccgagc tccagccgcagcctgagggg cccccgaggc tcctcctggg aggcctgcct 9780 gagtctggca ccatttacaacttcagtggc tgcatcagca acgtcttcgt gcagcggctc 9840 ctgggcccac agcgcgtatttgatctgcag cagaacctgg gcagcgtcaa tgtgagcacg 9900 ggctgtgcac ccgccctgcaagcccagacc ccgggcctgg ggcctagagg actgcaggcc 9960 accgcccgga aggcctcccgccgcagccgt cagcccgccc ggcatcctgc ctgcatgctg 10020 cccccacacc tcaggaccacccgagactcc taccagtttg ggggttccct gtccagtcac 10080 ctggagtttg tgggcatcctggcccgacat aggaactggc ccagtctctc catgcacgtc 10140 ctcccgcgaa gctcccgaggcctcctcctc ttcactgccc gtctgaggcc cggcagcccc 10200 tccctggcgc tcttcctgagcaatggccac ttcgttgcac agatggaagg cctcgggact 10260 cggctccgcg cccagagccgccagcgctcc cggcctggcc gctggcacaa ggtctccgtg 10320 cgctgggaga agaaccggatcctgctggtg acggacgggg cccgggcctg gagccaggag 10380 gggccgcacc ggcagcaccagggggcagag cacccccagc cccacaccct ctttgtgggc 10440 ggcctcccgg ccagcagccacagctccaaa cttccggtga ccgtcgggtt cagcggctgt 10500 gtgaagagac tgaggctgcacgggaggccc ctgggggccc ccacacggat ggcaggggtc 10560 acaccctgca tcttgggccccctggaggcg ggcctgttct tcccaggcag cgggggagtt 10620 atcactttag acctcccaggagctacactg cctgatgtgg gcctggaact ggaggtgcgg 10680 cccctggcag tcaccggactgatcttccac ttgggccagg cccggacgcc cccctacttg 10740 cagttgcagg tgaccgagaagcaagtcctg ctgcgggcgg atgacggagc aggggagttc 10800 tccacgtcag tgacccgcccctcagtgctg tgtgatggcc agtggcaccg gctagcggtg 10860 atgaaaagcg ggaatgtgctccggctggag gtggacgcgc agagcaacca caccgtgggc 10920 cccttgctgg cggctgcagctggtgcccca gcccctctgt acctcggggg cctgcctgag 10980 cccatggccg tgcagccctggccccccgcc tactgcggct gcatgaggag gctggcggtg 11040 aaccggtccc ccgtcgccatgactcgctct gtggaggtcc acggggcagt gggggccagt 11100 ggctgcccag ccgcctag11118 9 11091 DNA Homo sapiens 9 atggcgaagc ggctctgcgc ggggagcgcactgtgtgttc gcggcccccg gggccccgcg 60 ccgctgctgc tggtcgggct ggcgctgctgggcgcggcgc gggcgcggga ggaggcgggc 120 ggcggcttca gcctgcaccc gccctacttcaacctggccg agggcgcccg catcgccgcc 180 tccgcgacct gcggagagga ggccccggcgcgcggctccc cgcgccccac cgaggacctt 240 tactgcaagc tggtaggggg ccccgtggccggcggcgacc ccaaccagac catccggggc 300 cagtactgtg acatctgcac ggctgccaacagcaacaagg cacaccccgc gagcaatgcc 360 atcgatggca cggagcgctg gtggcagagtccaccgctgt cccgcggcct ggagtacaac 420 gaggtcaacg tcaccctgga cctgggccaggtcttccacg tggcctacgt cctcatcaag 480 tttgccaact caccccggcc ggacctctgggtgctggagc ggtccatgga cttcggccgc 540 acctaccagc cctggcagtt ctttgcctcctccaagaggg actgtctgga gcggttcggg 600 ccacagacgc tggagcgcat cacacgggacgacgcggcca tctgcaccac cgagtactca 660 cgcatcgtgc ccctggagaa cggagagatcgtggtgtccc tggtgaacgg acgtccgggc 720 gccatgaatt tctcctactc gccgctgctacgtgagttca ccaaggccac caacgtccgc 780 ctgcgcttcc tgcgtaccaa cacgctgctgggccatctca tggggaaggc gctgcgggac 840 cccacggtca cccgccggta ttattacagcatcaaggata tcagcatcgg aggccgctgt 900 gtctgccacg gccacgcgga tgcctgcgatgccaaagacc ccacggaccc gttcaggctg 960 cagtgcacct gccagcacaa cacctgcgggggcacctgcg accgctgctg ccccggcttc 1020 aatcagcagc cgtggaagcc tgcgactgccaacagtgcca acgagtgcca gtcctgtaac 1080 tgctacggcc atgccaccga ctgttactacgaccctgagg tggaccggcg ccgcgccagc 1140 cagagcctgg atggcaccta tcagggtgggggtgtctgta tcgactgcca gcaccacacc 1200 accggcgtca actgtgagcg ctgcctgcccggcttctacc gctctcccaa ccaccctctc 1260 gactcgcccc acgtctgccg ccgctgcaactgcgagtccg acttcacgga tggcacctgc 1320 gaggacctga cgggtcgatg ctactgccggcccaacttct ctggggagcg gtgtgacgtg 1380 tgtgccgagg gcttcacggg cttcccaagctgctacccga cgccctcgtc ctccaatgac 1440 accagggagc aggtgctgcc agccggccagattgtgaatt gtgactgcag cgcggcaggg 1500 acccagggca acgcctgccg gaaggacccaagggtgggac gctgtctgtg caaacccaac 1560 ttccaaggca cccattgtga gctctgcgcgccagggttct acggccccgg ctgccagccc 1620 tgccagtgtt ccagccctgg agtggccgatgaccgctgtg accctgacac aggccagtgc 1680 aggtgccgag tgggcttcga gggggccacatgtgatcgct gtgcccccgg ctactttcac 1740 ttccctctct gccagttgtg tggctgcagccctgcaggaa ccttgcccga gggctgcgat 1800 gaggccggcc gctgcctatg ccagcctgagtttgctggac ctcattgtga ccggtgccgc 1860 cctggctacc atggtttccc caactgccaagcatgcacct gcgaccctcg gggagccctg 1920 gaccagctct gtggggcggg aggtttgtgccgctgccgcc ccggctacac aggcactgcc 1980 tgccaggaat gcagccccgg ctttcacggcttccccagct gtgtcccctg ccactgctct 2040 gctgaaggct ccctgcacgc agcctgtgacccccggagtg ggcagtgcag ctgccggccc 2100 cgtgtgacgg ggctgcggtg tgacacatgtgtgcccggtg cctacaactt cccctactgc 2160 gaagctggct cttgccaccc tgccggtctggccccagtgg atcctgccct tcctgaggca 2220 caggttccct gtatgtgccg ggctcacgtggaggggccga gctgtgaccg ctgcaaacct 2280 gggttctggg gactgagccc cagcaaccccgagggctgta cccgctgcag ctgcgacctc 2340 aggggcacac tgggtggagt tgctgagtgccagccgggca ccggccagtg cttctgcaag 2400 ccccacgtgt gcggccaggc ctgcgcgtcctgcaaggatg gcttctttgg actggatcag 2460 gctgactatt ttggctgccg cagctgccggtgtgacattg gcggtgcact gggccagagc 2520 tgtgaaccga ggacgggcgt ctgccggtgccgccccaaca cccagggccc cacctgcagc 2580 gagcctgcga gggaccacta cctcccggacctgcaccacc tgcgcctgga gctggaggag 2640 gctgccacac ctgagggtca cgccgtgcgctttggcttca accccctcga gttcgagaac 2700 ttcagctgga ggggctacgc gcagatggcacctgtccagc ccaggatcgt ggccaggctg 2760 aacctgacct cccctgacct tttctggctcgtcttccgat acgtcaaccg gggggccatg 2820 agtgtgagcg ggcgggtctc tgtgcgagaggagggcaggt cggccacctg cgccaactgc 2880 acagcacaga gtcagcccgt ggccttcccacccagcacgg agcctgcctt catcaccgtg 2940 ccccagaggg gcttcggaga gccctttgtgctgaaccctg gcacctgggc cctgcgtgtg 3000 gaggccgaag gggtgctcct ggactacgtggttctgctgc ctagcgcata ctacgaggcg 3060 gcgctcctgc agctgcgggt gactgaggcctgcacatacc gtccctctgc ccagcagtct 3120 ggcgacaact gcctcctcta cacacacctccccctggatg gcttcccctc ggccgccggg 3180 ctggaggccc tgtgtcgcca ggacaacagcctgccccggc cctgccccac ggagcagctc 3240 agcccgtcgc acccgccact gatcacctgcacgggcagtg atgtggacgt ccagcttcaa 3300 gtggcagtgc cacagccagg ccgctatgccctagtggtgg agtacgccaa tgaggatgcc 3360 cgccaggagg tgggcgtggc cgtgcacaccccacagcggg ccccccagca ggggctgctc 3420 tccctgcacc cctgcctgta cagcaccctgtgccggggca ctgcccggga tacccaggac 3480 cacctggctg tcttccacct ggactcggaggccagcgtga ggctcacagc cgaacaggca 3540 cgcttcttcc tgcacggggt cactctggtgcccattgagg agttcagccc ggagttcgtg 3600 gagccccggg tcagctgcat cagcagccacggcgcctttg gccccaacag tgccgcctgt 3660 ctgccctcgc gcttcccaaa gccgccccagcccatcatcc tcagggactg ccaggtgatc 3720 ccgctgccgc ccggcctccc gctgacccacgcgcaggatc tcactccagc catgtcccca 3780 gctggacccc gacctcggcc ccccaccgctgtggaccctg atgcagagcc caccctgctg 3840 cgtgagcccc aggccaccgt ggtcttcaccacccatgtgc ccacgctggg ccgctatgcc 3900 ttcctgctgc acggctacca gccagcccaccccaccttcc ccgtggaagt cctcatcaac 3960 gccggccgcg tgtggcaggg ccacgccaacgccagcttct gtccacatgg ctacggctgc 4020 cgcaccctgg tggtgtgtga gggccaggccctgctggacg tgacccacag cgagctcact 4080 gtgaccgtgc gtgtgcccaa gggccggtggctctggctgg attatgtact cgtggtccct 4140 gagaacgtct acagctttgg ctacctccgggaggagcccc tggataaatc ctatgacttc 4200 atcagccact gcgcagccca gggctaccacatcagcccca gcagctcatc cctgttctgc 4260 cgaaacgctg ctgcttccct ctccctcttctataacaacg gagcccgtcc atgtggctgc 4320 cacgaagtag gtgctacagg ccccacgtgtgagcccttcg ggggccagtg tccctgccat 4380 gcccatgtca ttggccgtga ctgctcccgctgtgccaccg gatactgggg cttccccaac 4440 tgcaggccct gtgactgcgg tgcccgcctctgtgacgagc tcacgggcca gtgcatctgc 4500 ccgccacgca ccatcccgcc cgactgcctgctgtgccagc cccagacctt tggctgccac 4560 cccctggtcg gctgtgagga gtgtaactgctcagggcccg gcatccagga gctcacagac 4620 cctacctgtg acacagacag cggccagtgcaagtgcagac ccaacgtgac tgggcgccgc 4680 tgtgatacct gctctccggg cttccatggctacccccgct gccgcccctg tgactgtcac 4740 gaggcgggca ctgcgcctgg cgtgtgtgaccccctcacag ggcagtgcta ctgtaaggag 4800 aacgtgcagg gccccaaatg tgaccagtgcagccttggga ccttctcact ggatgctgcc 4860 aaccccaaag gttgcacccg ctgcttctgctttggggcca cggagcgctg ccggagctcg 4920 tcctacaccc gccaggagtt cgtggatatggagggatggg tgctgctgag cactgaccgg 4980 caggtggtgc cccacgagcg gcagccagggacggagatgc tccgtgcaga cctgcggcac 5040 gtgcctgagg ctgtgcccga ggctttccccgagctgtact ggcaggcccc accctcctac 5100 ctgggggacc gggtgtcatc ctacggtgggaccctccgtt atgaactgca ctcagagacc 5160 cagcggggag atgtctttgt ccccatggagagcaggccgg atgtggtgct gcagggcaac 5220 cagatgagca tcacattcct ggagccggcataccccacgc ctggccacgt tcaccgtggg 5280 cagctgcagc tggtggaggg gaacttccggcatacggaga cgcgcaacac tgtgtcccgc 5340 gaggagctca tgatggtgct ggccagcctggagcagctgc agatccgtgc cctcttctca 5400 cagatctcct cggctgtctt cctgcgcagggtggcactgg aggtggccag cccagcaggc 5460 cagggggccc tggccagcaa tgtggagctgtgcctgtgcc ccgccagcta ccggggggac 5520 tcatgccagg aatgtgcccc cggcttctatcgggacgtca aaggtctctt cctgggccga 5580 tgtgtccctt gtcagtgcca tggacactcagaccgctgcc tccctggctc tggcgtctgt 5640 gtggactgcc agcacaacac cgaaggggcccactgtgagc gctgccaggc tggcttcgtg 5700 agcagcaggg acgaccccag cgccccctgtgtcagctgcc cctgccccct ctcagtgcct 5760 tccaacaact tcgccgaggg ctgtgtcctgcgaggcggcc gcacccagtg cctctgcaaa 5820 cctggttatg caggtgcctc ctgcgagcggtgtgcgcccg gattctttgg gaacccactg 5880 gtgctgggca gctcctgcca gccatgcgactgcagcggca acggtgaccc caacttgctc 5940 ttcagcgact gcgaccccct gacgggcgcctgccgtggct gcctgcgcca caccactggg 6000 ccccgctgcg agatctgtgc ccccggcttctacggcaacg ccctgctgcc cggcaactgc 6060 acccggtgcg actgtacccc atgtgggacagaggcctgcg acccccacag cgggcactgc 6120 ctgtgcaagg cgggcgtgac tgggcggcgctgtgaccgct gccaggaggg acattttggt 6180 ttcgatggct gcgggggctg ccgcccgtgtgcttgtggac cggccgccga gggctccgag 6240 tgccaccccc agagcggaca gtgccactgccgaccaggga ccatgggacc ccagtgccgc 6300 gagtgtgccc ctggctactg ggggctccctgagcagggct gcaggcgctg ccagtgccct 6360 gggggccgct gtgaccctca cacgggccgctgcaactgcc ccccggggct cagcggggag 6420 cgctgcgaca cctgcagcca gcagcatcaggtgcctgttc caggcgggcc tgtgggccac 6480 agcatccact gtgaagtgtg tgaccactgtgtggtcctgc tcctggatga cctggaacgg 6540 gccggcgccc tcctccccgc cattcacgagcaactgcgtg gcatcaatgc cagctccatg 6600 gcctgggccc gtctgcacag gctgaacgcctccatcgctg acctgcagag ccagctccgg 6660 agccccctgg gcccccgcca tgagacggcacagcagctgg aggtgctgga gcagcagagc 6720 acaagcctcg ggcaggacgc acggcggctaggcggccagg cagccgtggg gacccgagac 6780 caggcgagcc aattgctggc cggcaccgaggccacactgg gccatgcgaa gacgctgttg 6840 gcggccatcc gggctgtgga ccgcaccctgagcgagctca tgtcccagac gggccacctg 6900 gggctggcca atgcctcggc tccatcaggtgagcagctgc tccggacact ggccgaggtg 6960 gagcggctgc tctgggagat gcgggcccgggacctggggg ccccgcaggc agcagctgag 7020 gctgagttgg ctgcagcaca gagattgctggcccgggtgc aggagcagct gagcagcctc 7080 tgggaggaga accaggcact ggccacacaaacccgcgacc ggctggccca gcacgaggcc 7140 ggcctcatgg acctgcgaga ggctttgaaccgggcagtgg acgccacacg ggaggcccag 7200 gagctcaaca gccgcaacca ggagcgcctggaggaagccc tgcaaaggaa gcaggagctg 7260 tcccgggaca atgccaccct gcaggccactctgcatgcgg ctagggacac cctggccagc 7320 gtcttcagat tgctgcacag cctggaccaggctaaggagg agctggagcg cctcgccgcc 7380 agcctggatg gggctcggac cccactgctgcagaggatgc agaccttctc cccggcgggc 7440 agcaagctgc gtctagtgga ggccgccgaggcccacgcac agcagctggg ccagctggca 7500 ctcaatctgt ccagcatcat cctggacgtcaaccaggacc gcctcaccca gagggccatc 7560 gaggcctcca acgcctacag ccgcatcctgcaggccgtgc aggctgccga ggatgctgct 7620 ggccaggccc tgcagcaggc ggaccacacgtgggcgacgg tggtgcggca gggcctggtg 7680 gaccgagccc agcagctcct ggccaacagcactgcactag aagaggccat gctccaggaa 7740 cagcagaggc tgggccttgt gtgggctgccctccagggtg ccaggaccca gctccgagat 7800 gtccgggcca agaaggacca gctggaggcgcacatccagg cggcgcaggc catgcttgcc 7860 atggacacag acgagacaag caagaagatcgcacatgcca aggctgtggc tgctgaagcc 7920 caggacaccg ccacccgtgt gcagtcccagctgcaggcca tgcaggagaa tgtggagcgg 7980 tggcagggcc agtacgaggg cctgcggggccaggacctgg gccaggcagt gcttgacgca 8040 ggccactcag tgtccaccct ggagaagacgctgccccagc tgctggccaa gctgagcatc 8100 ctggagaacc gtggggtgca caacgccagcctggccctgt ccgccagcat tggccgcgtg 8160 cgagagctca ttgcccaggc ccggggggctgccagtaagg tcaaggtgcc catgaagttc 8220 aacgggcgct caggggtgca gctgcgcaccccacgggatc ttgccgacct tgctgcctac 8280 actgccctca agttctacct gcagggcccagagcctgagc ctgggcaggg taccgaggat 8340 cgctttgtga tgtacatggg cagccgccaggccactgggg actacatggg tgtgtctctg 8400 cgtgacaaga aggtgcactg ggtgtatcagctgggtgagg cgggccctgc agtcctaagc 8460 atcgatgagg acattgggga gcagttcgcagctgtcagcc tggacaggac tctccagttt 8520 ggccacatgt ccgtcacagt ggagagacagatgatccagg aaaccaaggg tgacacggtg 8580 gcccctgggg cagaggggct gctcaacctgcggccagacg acttcgtctt ctacgtcggg 8640 gggtacccca gtaccttcac gccccctcccctgcttcgct tccccggcta ccggggctgc 8700 atcgagatgg acacgctgaa tgaggaggtggtcagcctct acaacttcga gaggaccttc 8760 cagctggaca cggctgtgga caggccttgtgcccgctcca agtcgaccgg ggacccgtgg 8820 ctcacggacg gctcctacct ggacggcaccggcttcgccc gcatcagctt cgacagtcag 8880 atcagcacca ccaagcgctt cgagcaggagctgcggctcg tgtcctacag cggggtgctc 8940 ttcttcctga agcagcagag ccagttcctgtgcttggccg tgcaagaagg cagcctcgtg 9000 ctgttgtatg actttggggc tggcctgaaaaaggccgtcc cactgcagcc cccaccgccc 9060 ctgacctcgg ccagcaaggc gatccaggtgttcctgctgg ggggcagccg caagcgtgtg 9120 ctggtgcgtg tggagcgggc cacggtgtacagcgtggagc aggacaatga tctggagctg 9180 gccgacgcct actacctggg gggcgtgccgcccgaccagc tgcccccgag cctgcgacgg 9240 ctcttcccca ccggaggctc agtccgtggctgcgtcaaag gcatcaaggc cctgggcaag 9300 tatgtggacc tcaagcggct gaacacgacaggcgtgagcg ccggctgcac cgccgacctg 9360 ctggtggggc gcgccatgac tttccatggccacggcttcc ttcgcctggc gctctcgaac 9420 gtggcaccgc tcactggcaa cgtctactccggcttcggct tccacagcgc ccaggacagt 9480 gccctgctct actaccgggc gtccccggatgggctatgcc aggtgtccct gcagcagggc 9540 cgtgtgagcc tacagctcct gaggactgaagtgaaaactc aagcgggctt cgccgatggt 9600 gccccccatt acgtcgcctt ctacagcaatgccacgggag tctggctgta tgtcgatgac 9660 cagctccagc agatgaagcc ccaccggggaccaccccccg agctccagcc gcagcctgag 9720 gggcccccga ggctcctcct gggaggcctgcctgagtctg gcaccattta caacttcagt 9780 ggctgcatca gcaacgtctt cgtgcagcggctcctgggcc cacagcgcgt atttgatctg 9840 cagcagaacc tgggcagcgt caatgtgagcacgggctgtg cacccgccct gcaagcccag 9900 accccgggcc tggggcctag aggactgcaggccaccgccc ggaaggcctc ccgccgcagc 9960 cgtcagcccg cccggcatcc tgcctgcatgctgcccccac acctcaggac cacccgagac 10020 tcctaccagt ttgggggttc cctgtccagtcacctggagt ttgtgggcat cctggcccga 10080 cataggaact ggcccagtct ctccatgcacgtcctcccgc gaagctcccg aggcctcctc 10140 ctcttcactg cccgtctgag gcccggcagcccctccctgg cgctcttcct gagcaatggc 10200 cacttcgttg cacagatgga aggcctcgggactcggctcc gcgcccagag ccgccagcgc 10260 tcccggcctg gccgctggca caaggtctccgtgcgctggg agaagaaccg gatcctgctg 10320 gtgacggacg gggcccgggc ctggagccaggaggggccgc accggcagca ccagggggca 10380 gagcaccccc agccccacac cctctttgtgggcggcctcc cggccagcag ccacagctcc 10440 aaacttccgg tgaccgtcgg gttcagcggctgtgtgaaga gactgaggct gcacgggagg 10500 cccctggggg cccccacacg gatggcaggggtcacaccct gcatcttggg ccccctggag 10560 gcgggcctgt tcttcccagg cagcgggggagttatcactt tagacctccc aggagctaca 10620 ctgcctgatg tgggcctgga actggaggtgcggcccctgg cagtcaccgg actgatcttc 10680 cacttgggcc aggcccggac gcccccctacttgcagttgc aggtgaccga gaagcaagtc 10740 ctgctgcggg cggatgacgg agcaggggagttctccacgt cagtgacccg cccctcagtg 10800 ctgtgtgatg gccagtggca ccggctagcggtgatgaaaa gcgggaatgt gctccggctg 10860 gaggtggacg cgcagagcaa ccacaccgtgggccccttgc tggcggctgc agctggtgcc 10920 ccagcccctc tgtacctcgg gggcctgcctgagcccatgg ccgtgcagcc ctggcccccc 10980 gcctactgcg gctgcatgag gaggctggcggtgaaccggt cccccgtcgc catgactcgc 11040 tctgtggagg tccacggggc agtgggggccagtggctgcc cagccgccta g 11091 10 1014 DNA Homo sapiens 10 atgacaaacaacagcggctc caaagccgaa ctcgttgtgg gagggaaata caaactggtg 60 cggaagatcgggtctggctc ctttggagac gtttatctgg gcatcaccac caccaacggc 120 gaggacgtagcagtgaagct ggaatctcag aaggtcaagc acccccagtt gctgtatgag 180 agcaaactctacacgattct tcaaggtggg gttggcatcc cccacatgca ctggtatggt 240 caggaaaaagacaacaatgt gctagtcatg gaccttctgg gacccagcct cgaagacctc 300 tttaatttctgttcaagaag gttcaccatg aaaactgtac ttatgttagc cgaccagatg 360 atcagcagaattgaatacgt gcatacaaag aattttctac accgagacat taaaccagat 420 aacttcctgatgggtactgg gcgtcactgt aataagttgt tccttattga ttttggtttg 480 gccaaaaagtacagagacaa caggaccagg caacacatac cgtacagaga agataaacac 540 ctcattggcactgtccgata tgccagcatc aatgcacatc ttggtattga gcagagccgc 600 cgagatgacatggaatcctt aggctacgtt ttcatgtatt ttaatagaac cagcctgccg 660 tggcaaggactaagggctat gacaaaaaaa caaaaatatg aaaagattag tgagaagaag 720 atgtccacccctgttgaagt tttatgtaag gggtttcctg cagaattcgc catgtacttg 780 aactactgtcgtgggctgcg ctttgaggaa gtcccagatt acatgtatct gaggcagcta 840 ttccgcattcttttcaggac cctgaaccac caatatgact acacatttga ttggacgatg 900 ttaaagcagaaagcagcaca gcaggcagcc tcttccagtg ggcagggtca gcaggcccaa 960 acccagacaggcaagcaaac tgaaaaaaac aagaataatg tgaaagataa ctaa 1014 11 2667 DNA Homosapiens 11 atggagtcgc tcctgctgcc ggtgctgctg ctgctggcca tactgtggacgcaggctgcc 60 gccctcatta atctcaagta ctcggtagaa gaggagcagc gcgccgggacggtgattgcc 120 aacgtggcca aagacgcgcg agaggcgggc ttcgcgctgg acccccggcaggcttcagcc 180 tttcgcgtgg tgtccaactc ggctccacac ctagtggaca tcaatcccagctctggcctg 240 ctggtcacca agcagaagat tgaccgtgat ctgctgtgcc gccagagccccaagtgcatc 300 atctcgctcg aggtcatgtc cagctcaatg gaaatctgcg tgataaaggtggagatcaag 360 gacctgaacg acaatgcgcc cagtttcccg gcagcacaga tcgagctggagatctcggag 420 gcagccagcc ctggcacgcg catcccgctg gacagcgctt acgatccagactcaggaagc 480 tttggcgtgc agacttacga gctcacgccc aacgagctgt tcggcctggagatcaagacg 540 cgcggcgacg gctcccgctt tgccgaactc gtggtggaaa agagcctggaccgcgagacg 600 cagtcgcact acagcttccg aatcactgcg ctagacggtg gcgacccgccgcgcctgggc 660 accgttggcc ttagtatcaa ggtgaccgac tccaatgaca acaacccggtgtttagcgag 720 tccacctacg cggtgagcgt gccagaaaac tcgcctccca acacacccgtcatccgcctc 780 aacgccagcg atccagacga gggcaccaac ggccaggtgg tctactccttctatggctac 840 gtcaacgacc gcacgcgcga gctctttcag atcgacccgc acagtggcctggtcactgtc 900 actggcgctt tagactacga agaggggcac gtgtacgaac tggacgtgcaggctaaggac 960 ttggggccca attccatccc ggcacactgc aaggtcaccg tcagcgtgctggacaccaat 1020 gacaatccgc cggtcatcaa cctgctgtca gtcaacagtg agcttgtggaggtcagcgag 1080 agcgcccccc cgggctacgt gatcgccttg gtgcgggtgt ctgatcgcgactcaggcctc 1140 aatggacgtg tgcagtgccg tttgctgggc aatgtgccct ttcgactgcaggaatatgag 1200 agcttctcca ctattctggt ggacggacgg ctggaccgcg agcagcacgaccaatacaac 1260 ctcacaattc aggcacgcga cggcggcgtg cccatgctgc agagtgccaagtcctttacc 1320 gtgctcatca ctgacgaaaa tgacaaccac ccgcactttt ccaagccctactaccaggtc 1380 attgtgcagg agaacaacac gcctggcgcc tatctgctct ctgtgtctgctcgcgacccc 1440 gacctgggtc tcaacggcag tgtctcctac cagatcgtgc cgtcgcaggtgcgggacatg 1500 cctgtcttca cctatgtctc catcaatccc aactcaggcg acatctacgcgctgcgatcc 1560 tttaaccacg agcagaccaa ggcgttcgaa ttcaaggtgc tggccaaggacggcggcctt 1620 ccctcactgc aaagcaacgc tacggtgcgg gtcatcatcc tcgacgtcaacgacaacacc 1680 ccggtcatca cagccccacc tctgattaac ggcactgccg aggtctacataccccgcaac 1740 tctggcatag gctacctggt gactgttgtc aaggcagaag actacgatgagggcgaaaat 1800 ggccgagtca cctacgacat gaccgagggc gaccgcggct tctttgaaatagaccaggtc 1860 aatggcgaag tcagaaccac ccgcaccttc ggggagagct ccaagtcctcctatgagctt 1920 atcgtggtgg ctcacgacca cggcaagaca tctctctctg cctctgctctcgtcctaatc 1980 tacttgtccc ctgctctcga tgcccaagag tcaatgggct ctgtgaacttgtccttgatt 2040 ttcattattg ccctgggctc cattgcgggc atcctctttg taactatgatcttcgtggca 2100 atcaagtgca agcgagacaa caaagagatc cggacctaca actgcagtaattgtttaacc 2160 atcacttgtc tcctcggctg ttttataaaa ggacaaaaca gcaagtgtctgcattgcatc 2220 tcggtttctc ccattagcga ggagcaagac aaaaagacag aggagaaagtgagcctaagg 2280 ggaaagagaa ttgctgagta ctcctatggg catcaaaaga aatcaagcaagaagaaaaaa 2340 atcagtaaga atgacatccg cctggtaccc cgggatgtgg aggagacagacaagatgaac 2400 gttgtcagtt gctcttccct gacctcctcc ctcaactatt ttgactaccaccagcagacg 2460 ctgcccctgg gctgccgccg ctctgagagc actttcctga atgtggagaaccagaatacc 2520 cgcaacacca gtgctaacca catctaccat cactctttca acagccaggggccccagcag 2580 cctgacctga ttatcaacgg tgtgcctctg cctgaggtga gtgcagctaagtggctctgt 2640 gaggttctcc caggtctcct tctttag 2667 12 2568 DNA Homosapiens 12 atggagtcgc tcctgctgcc ggtgctgctg ctgctggcca tactgtggacgcaggctgcc 60 gccctcatta atctcaagta ctcggtagaa gaggagcagc gcgccgggacggtgattgcc 120 aacgtggcca aagacgcgcg agaggcgggc ttcgcgctgg acccccggcaggcttcagcc 180 tttcgcgtgg tgtccaactc ggctccacac ctagtggaca tcaatcccagctctggcctg 240 ctggtcacca agcagaagat tgaccgtgat ctgctgtgcc gccagagccccaagtgcatc 300 atctcgctcg aggtcatgtc cagctcaatg gaaatctgcg tgataaaggtggagatcaag 360 gacctgaacg acaatgcgcc cagtttcccg gcagcacaga tcgagctggagatctcggag 420 gcagccagcc ctggcacgcg catcccgctg gacagcgctt acgatccagactcaggaagc 480 tttggcgtgc agacttacga gctcacgccc aacgagctgt tcggcctggagatcaagacg 540 cgcggcgacg gctcccgctt tgccgaactc gtggtggaaa agagcctggaccgcgagacg 600 cagtcgcact acagcttccg aatcactgcg ctagacggtg gcgacccgccgcgcctgggc 660 accgttggcc ttagtatcaa ggtgaccgac tccaatgaca acaacccggtgtttagcgag 720 tccacctacg cggtgagcgt gccagaaaac tcgcctccca acacacccgtcatccgcctc 780 aacgccagcg atccagacga gggcaccaac ggccaggtgg tctactccttctatggctac 840 gtcaacgacc gcacgcgcga gctctttcag atcgacccgc acagtggcctggtcactgtc 900 actggcgctt tagactacga agaggggcac gtgtacgaac tggacgtgcaggctaaggac 960 ttggggccca attccatccc ggcacactgc aaggtcaccg tcagcgtgctggacaccaat 1020 gacaatccgc cggtcatcaa cctgctgtca gtcaacagtg agcttgtggaggtcagcgag 1080 agcgcccccc cgggctacgt gatcgccttg gtgcgggtgt ctgatcgcgactcaggcctc 1140 aatggacgtg tgcagtgccg tttgctgggc aatgtgccct ttcgactgcaggaatatgag 1200 agcttctcca ctattctggt ggacggacgg ctggaccgcg agcagcacgaccaatacaac 1260 ctcacaattc aggcacgcga cggcggcgtg cccatgctgc agagtgccaagtcctttacc 1320 gtgctcatca ctgacgaaaa tgacaaccac ccgcactttt ccaagccctactaccaggtc 1380 attgtgcagg agaacaacac gcctggcgcc tatctgctct ctgtgtctgctcgcgacccc 1440 gacctgggtc tcaacggcag tgtctcctac cagatcgtgc cgtcgcaggtgcgggacatg 1500 cctgtcttca cctatgtctc catcaatccc aactcaggcg acatctacgcgctgcgatcc 1560 tttaaccacg agcagaccaa ggcgttcgaa ttcaaggtgc tggccaaggacggcggcctt 1620 ccctcactgc aaagcaacgc tacggtgcgg gtcatcatcc tcgacgtcaacgacaacacc 1680 ccggtcatca cagccccacc tctgattaac ggcactgccg aggtctacataccccgcaac 1740 tctggcatag gctacctggt gactgttgtc aaggcagaag actacgatgagggcgaaaat 1800 ggccgagtca cctacgacat gaccgagggc gaccgcggct tctttgaaatagaccaggtc 1860 aatggcgaag tcagaaccac ccgcaccttc ggggagagct ccaagtcctcctatgagctt 1920 atcgtggtgg ctcacgacca cggcaagaca tctctctctg cctctgctctcgtcctaatc 1980 tacttgtccc ctgctctcga tgcccaagag tcaatgggct ctgtgaacttgtccttgatt 2040 ttcattattg ccctgggctc cattgcgggc atcctctttg taactatgatcttcgtggca 2100 atcaagtgca agcgagacaa caaagagatc cggacctaca actgcagaattgctgagtac 2160 tcctatgggc atcaaaagaa atcaagcaag aagaaaaaaa tcagtaagaatgacatccgc 2220 ctggtacccc gggatgtgga ggagacagac aagatgaacg ttgtcagttgctcttccctg 2280 acctcctccc tcaactattt tgactaccac cagcagacgc tgcccctgggctgccgccgc 2340 tctgagagca ctttcctgaa tgtggagaac cagaataccc gcaacaccagtgctaaccac 2400 atctaccatc actctttcaa cagccagggg ccccagcagc ctgacctgattatcaacggt 2460 gtgcctctgc ctgagactga aaactattct tttgactcca actacgtgaatagccgagcc 2520 catttaatca agaggtatgt tggtttgctt gcttattgct gcaactaa2568 13 990 DNA Homo sapiens 13 atggtgacga aggcctttgt cttgttggccatctttgcag aagcctctgc aaaatcgtgt 60 gctccaaata aagcagatgt cattcttgtgttttgctatc ccaaaaccat catcaccaaa 120 atccccgagt gtccctatgg atgggaagttcatcagctgg ccctcggagg gctgtgttac 180 aatggggtcc acgaaggagg ttactaccaatttgtgatcc cagatttatc acctaaaaac 240 aagtcctatt gtggaaccca gtctgagtacaagccaccta tctatcactt ctacagtcac 300 atcgtttcca atgacaccac agtgattgtaaaaaaccagc ctgtcaacta ctccttctcc 360 tgcacctacc actccaccta cttggtgaaccaggctgcct ttgaccagag agtggccact 420 gttcacgtga agaacgggag catgggcacatttgagagcc aactgtctct caacttctac 480 actaatgcca agttctccat caagaaagaagctccctttg tcctggaggc atccgaaatc 540 ggttcagatc tgtttgcagg agtggaagccaaagggttaa gcattaggtt taaagtggtc 600 ttgaacagct gttgggccac cccctcggctgacttcatgt atcccttgca gtggcagctg 660 atcaacaagg gctgccccac ggatgaaaccgtcctcgtgc atgagaatgg gagagatcac 720 agggcaacct tccaattcaa tgctttccggttccagaaca tccccaaact ctccaaggtg 780 tggttacact gtgagacgtt catctgcgacagtgagaaac tctcctgccc agtgacctgc 840 gataaacgga agcgcctcct gcgagaccagaccgggggag tcctggtcgt ggagctctcc 900 ctgcggagca ggggattttc cagtctctatagcttctcag atgttctcca ccacctcatc 960 atgatgttgg ggatttgtgc cgtgttatag990 14 699 DNA Homo sapiens 14 atgctctaca caaggaaaaa cctgacctgcgcacaaacca tcaactcctc agcttttggg 60 aacttgaatg tgaccaagaa aaccaccttcattgtccatg gattcaggcc aacaggctcc 120 cctcctgttt ggatggatga cttagtaaagggtttgctct ctgttgaaga catgaacgta 180 gttgttgttg attggaatcg aggagctacaactttaatat atacccatgc ctctagtaag 240 accagaaaag tagccatggt cttgaaggaatttattgacc agatgttggc agaaggagct 300 tctcttgatg acatttacat gatcggagtaagtctaggag cccacatatc tgggtttgtt 360 ggagagatgt acgatggatg gctggggagaattacaggcc tcgaccctgc aggcccttta 420 ttcaacggga aacctcacca agacagattagatcccagtg atgcgcagtt tgttgatgtc 480 atccattccg acactgatgg taacgctcctttccttgtgg cactgggcta caaggagcca 540 ttaggaaaca tagacttcta cccaaatggaggattggatc aacctggctg ccccaaaaca 600 atattgggag gaaatgttaa ggaaatgatacaggcttcct atatcttttt ccttaaaaac 660 gactctatgg acttaagttc accgaaggaagtggaatga 699 15 1359 DNA Homo sapiens 15 atgttgagat tctacttattcatcagtttg ttgtgcttgt caagatcaga cgcagaagaa 60 acatgtcctt cattcaccaggctgagcttt cacagtgcag tggttggtac gggactaaat 120 gtgaggctga tgctctacacaaggaaaaac ctgacctgcg cacaaaccat caactcctca 180 gcttttggga acttgaatgtgaccaagaaa accaccttca ttgtccatgg attcaggcca 240 acaggctccc ctcctgtttggatggatgac ttagtaaagg gtttgctctc tgttgaagac 300 atgaacgtag ttgttgttgattggaatcga ggagctacaa ctttaatata tacccatgcc 360 tctagtaaga ccagaaaagtagccatggtc ttgaaggaat ttattgacca gatgttggca 420 gaaggagctt ctcttgatgacatttacatg atcggagtaa gtctaggagc ccacatatct 480 gggtttgttg gagagatgtacgatggatgg ctggggagaa ttacaggcct cgaccctgca 540 ggccctttat tcaacgggaaacctcaccaa gacagattag atcccagtga tgcgcagttt 600 gttgatgtca tccattccgacactgatgca ctgggctaca aggagccatt aggaaacata 660 gacttctacc caaatggaggattggatcaa cctggctgcc ccaaaacaat attgggagga 720 tttcagtatt ttaaatgtgaccaccagagg tctgtatacc tgtacctgtc ttccctgaga 780 gagagctgca ccatcactgcgtatccctgt gactcctacc aggattatag gaatggcaag 840 tgtgtcagct gcggcacgtcacaaaaagag tcctgtcccc ttctgggcta ttatgctgat 900 aattggaaag accatctaagggggaaagat cctccaatga cgaaggcatt ctttgacaca 960 gctgaggaga gcccattctgcatgtatcat tactttgtgg atattataac atgggacaag 1020 aatgtaagaa gaggggacattaccatcaaa ttgagagaca aagctggaaa cacccacaga 1080 tccaaaatca tcagtaatgaacccaccaca tttcagaaat atcaccaagt gagtctactt 1140 gcaagattta atcaagatctggataaagtg gctgcaattt ccttgatgtt ctctacagga 1200 tctctaatag gcccaaggtacaagctcagg attctccgaa tgaagttaag gtcccttgcc 1260 catccggaga ggcctcagctgtgtcggtat gatcttgtcc tgatggaaaa cgttgaaaca 1320 gtcttccaac ctattctttgcccagagttg cagttgtaa 1359 16 1353 DNA Homo sapiens 16 atggggctccggagccacca cctcagcctg ggccttctgc ttctgtttct actccctgca 60 gagtgcctgggagctgaggg ccggctggct ctcaagctgt tccgtgacct ctttgccaac 120 tacacaagtgccctgagacc tgtggcagac acagaccaga ctctgaatgt gaccctggag 180 gtgacactgtcccagatcat cgacatggat gaacggaacc aggtgctgac cctgtatctg 240 tggatacggcaggagtggac agatgcctac ctacgatggg accccaatgc ctatggtggc 300 ctggatgccatccgcatccc cagcagtctt gtgtggcggc cagacatcgt actctataac 360 aaagccgacgcgcagcctcc aggttccgcc agcaccaacg tggtcctgcg ccacgatggc 420 gccgtgcgctgggacgcgcc ggccatcacg cgcagctcgt gccgcgtgga tgtagcagcc 480 ttcccgttcgacgcccagca ctgcggcctg acgttcggct cctggactca cggcgggcac 540 caactggatgtgcggccgcg cggcgctgca gccagcctgg cggacttcgt ggagaacgtg 600 gagtggcgcgtgctgggcat gccggcgcgg cggcgcgtgc tcacctacgg ctgctgctcc 660 gagccctaccccgacgtcac cttcacgctg ctgctgcgcc gccgcgccgc cgcctacgtg 720 tgcaacctgctgctgccctg cgtgctcatc tcgctgcttg cgccgctcgc cttccacctg 780 cctgccgactcaggcgagaa ggtgtcgctg ggcgtcaccg tgctgctggc gctcaccgtc 840 ttccagttgctgctggccga gagcatgcca ccggccgaga gcgtgccgct catcgggaag 900 tactacatggccactatgac catggtcaca ttctcaacag cactcaccat ccttatcatg 960 aacctgcattactgtggtcc cagtgtccgc ccagtgccag cctgggctag ggccctcctg 1020 ctgggacacctggcacgggg cctgtgcgtg cgggaaagag gggagccctg tgggcagtcc 1080 aggccacctgagttatctcc tagcccccag tcgcctgaag gaggggctgg ccccccagcg 1140 ggcccttgccacgagccacg atgtctgtgc cgccaggaag ccctactgca ccacgtagcc 1200 accattgccaataccttccg cagccaccga gctgcccagc gctgccatga ggactggaag 1260 cgcctggcccgtgtgatgga ccgcttcttc ctggccatct tcttctccat ggccctggtc 1320 atgagcctcctggtgctggt gcaggccctg tga 1353 17 768 DNA Homo sapiens 17 atggttaagggtgagaaagg ccccaagggc aagaagatca ccctcaaggt ggccaggaat 60 tgcatcaaaatcacttttga tgggaaaaag cgccttgact tgagcaagat gggaattacc 120 accttccccaagtgtattct gcgccttagt gacatggacg agctggacct tagccggaat 180 cttatcaggaagatccctga ctccatctcc aagttccaga acctccggtg gctggacctg 240 cacagcaactacatagacaa gctgcctgag tccattggcc agatgaccag cctgctctac 300 ctcaacgtcagcaacaaccg gctgaccagc aacgggctgc ccgtggagct gaagcaactc 360 aagaacatccgcgctgtgaa cctaggcttg aaccacctgg acagcgtgcc caccacactg 420 ggggccctgaaggagctcca cgaggtaggg ctccatgaca acctactgaa caacatcccc 480 gtgagcatctccaagctccc caagctgaaa aagctcaaca taaagcggaa cccctttcca 540 aagccaggtgagtcggaaat attcatagac tccatcagga ggctggagaa cttgtatgtt 600 gtggaggagaaggatctgtg tgcggcttgc ctgagaaaat gccaaaacgc ccgggacaac 660 ctgaatagaatcaagaacat ggccacgacg acaccgagaa agaccatctt tcccaatctg 720 atctcacccaattccatggc caaggactcc tgggaagact ggaggtga 768 18 645 DNA Homo sapiens 18atgcaggcag gaactcagtc aacgcatgag tctctgaagc ctcagagggt acaatttcag 60tcccgaaatt ttcacaacat tttgcaatgg cagcctggga gggcacttac tggcaacagc 120agtgtctatt ttgtgcagta caaaatatat ggacagagac aatggaaaaa taaagaagac 180tgttggggta ctcaagaact ctcttgtgac cttaccagtg aaacctcaga catacaggaa 240ccttattacg ggagggtgag ggcggcctcg gctgggagct actcagaatg gagcatgacg 300ccgcggttca ctccctggtg ggaaacaaaa atagatcctc cagtcatgaa tataacccaa 360gtcaatggct ctttgttggt aattctccat gctccaaatt taccatatag ataccaaaag 420gaaaaaaatg tatctataga agattactat gaactactat accgagtttt tataattaac 480aattcactag aaaaggagca aaaggtttat gaaggggctc acagagcggt tgaaattgaa 540gctctaacac cacactccag ctactgtgta gtggctgaaa tatatcagcc catgttagac 600agaagaagtc agagaagtga agagagatgt gtggaaattc catga 645 19 696 DNA Homosapiens 19 atgatgccta aacattgctt tctaggcttc ctcatcagtt tcttccttactggtgtagca 60 ggaactcagt caacgcatga gtctctgaag cctcagaggg tacaatttcagtcccgaaat 120 tttcacaaca ttttgcaatg gcagcctggg agggcactta ctggcaacagcagtgtctat 180 tttgtgcagt acaaaatata tggacagaga caatggaaaa ataaagaagactgttggggt 240 actcaagaac tctcttgtga ccttaccagt gaaacctcag acatacaggaaccttattac 300 gggagggtga gggcggcctc ggctgggagc tactcagaat ggagcatgacgccgcggttc 360 actccctggt gggaaacaaa aatagatcct ccagtcatga atataacccaagtcaatggc 420 tctttgttgg taattctcca tgctccaaat ttaccatata gataccaaaaggaaaaaaat 480 gtatctatag aagattacta tgaactacta taccgagttt ttataattaacaattcacta 540 gaaaaggagc aaaaggttta tgaaggggct cacagagcgg ttgaaattgaagctctaaca 600 ccacactcca gctactgtgt agtggctgaa atatatcagc ccatgttagacagaagaagt 660 cagagaagtg aagagagatg tgtggaaatt ccatga 696 20 792 DNAHomo sapiens 20 atgatgccta aacattgctt tctaggcttc ctcatcagtt tcttccttactggtgtagca 60 ggaactcagt caacgcatga gtctctgaag cctcagaggg tacaatttcagtcccgaaat 120 tttcacaaca ttttgcaatg gcagcctggg agggcactta ctggcaacagcagtgtctat 180 tttgtgcagt acaaaatcat gttctcatgc agcatgaaaa gctctcaccagaagccaagt 240 ggatgctggc agcacatttc ttgtaacttc ccaggctgca gaacattggctaaatatgga 300 cagagacaat ggaaaaataa agaagactgt tggggtactc aagaactctcttgtgacctt 360 accagtgaaa cctcagacat acaggaacct tattacggga gggtgagggcggcctcggct 420 gggagctact cagaatggag catgacgccg cggttcactc cctggtgggaaacaaaaata 480 gatcctccag tcatgaatat aacccaagtc aatggctctt tgttggtaattctccatgct 540 ccaaatttac catatagata ccaaaaggaa aaaaatgtat ctatagaagattactatgaa 600 ctactatacc gagtttttat aattaacaat tcactagaaa aggagcaaaaggtttatgaa 660 ggggctcaca gagcggttga aattgaagct ctaacaccac actccagctactgtgtagtg 720 gctgaaatat atcagcccat gttagacaga agaagtcaga gaagtgaagagagatgtgtg 780 gaaattccat ga 792 21 780 DNA Homo sapiens 21 atgtatgtattatctccagt ggaatttata attctacaac ttttatttat tcaggccatt 60 tccagcagtttaaaaggttt cctttcagct atgagactgg ctcatagagg ctgtaatgtt 120 gatacaccagtttcaacgct cacaccagtg aagacttcag aatttgaaaa ctttaaaact 180 aaaatggttatcacatccaa aaaagactat cctctaagta agaattttcc atattccttg 240 gaacatcttcagacttctta ctgtgggctt gtccgagttg atatgcgtat gctttgctta 300 aaaagccttaggaaattaga cttgagtcac aaccatataa aaaagcttcc agctacaatt 360 ggagacctcatacaccttca agaacttaac ctgaatgaca atcacttgga gtcatttagt 420 gtagccttgtgtcattctac actccagaag tcacttcgga gtttggacct cagcaagaac 480 aaaatcaaggcactccctgt gcagttttgc cagctccagg aacttaagaa tttaaaactt 540 gacgataatgaattgattca atttccttgc aagataggac aactaataaa ccttcgcttt 600 ttgtcagcagctcgaaataa gcttccattt ttgcctagtg aatttagaaa tttatccctt 660 gaatacttggatctttttgg aaatactttt gaacaaccaa aagtccttcc agtaataaag 720 ctgcaagcaccattaacttt attggaatct tctgcacgaa ccatattaca taataggtaa 780 22 1251 DNAHomo sapiens 22 atgaagctac actgtgaggt ggaggtgatc agccggcact tgcccgccttggggcttagg 60 aaccggggca agggcgtccg agccgtgttg agcctctgtc agcagacttccaggagtcag 120 ccgccggtcc gagccttcct gctcatctcc accctgaagg acaagcgcgggacccgctat 180 gagctaaggg agaacattga gcaattcttc accaaatttg tagatgaggggaaagccact 240 gttcggttaa aggagcctcc tgtggatatc tgtctaagta aggccatttccagcagttta 300 aaaggtttcc tttcagctat gagactggct catagaggct gtaatgttgatacaccagtt 360 tcaacgctca caccagtgaa gacttcagaa tttgaaaact ttaaaactaaaatggttatc 420 acatccaaaa aagactatcc tctaagtaag aattttccat attccttggaacatcttcag 480 acttcttact gtgggcttgt ccgagttgat atgcgtatgc tttgcttaaaaagccttagg 540 aaattagact tgagtcacaa ccatataaaa aagcttccag ctacaattggagacctcata 600 caccttcaag aacttaacct gaatgacaat cacttggagt catttagtgtagccttgtgt 660 cattctacac tccagaagtc acttcggagt ttggacctca gcaagaacaaaatcaaggca 720 ctccctgtgc agttttgcca gctccaggaa cttaagaatt taaaacttgacgataatgaa 780 ttgattcaat ttccttgcaa gataggacaa ctaataaacc ttcgctttttgtcagcagct 840 cgaaataagc ttccattttt gcctagtgaa tttagaaatt tatcccttgaatacttggat 900 ctttttggaa atacttttga acaaccaaaa gtccttccag taataaagctgcaagcacca 960 ttaactttat tggaatcttc tgcacgaacc atattacata ataggaataggattccatat 1020 ggctctcata tcattccatt ccatctctgc caagatttgg ataccgcaaaaatttgtgtt 1080 tgtggaagat tctgtctgaa ctctttcatt caaggaacta ctaccatgaatctgcattct 1140 gttgcccaca ctgtggtctt agtagataat ttgggtggta ctgaagcacctattatctct 1200 tatttctgtt ctctaggctg ttatgttaat tcctctgata tgttaaagta a1251 23 461 PRT Homo sapiens 23 Met Leu Gly Ile Trp Ile Val Ala Phe LeuPhe Phe Gly Thr Ser Arg 1 5 10 15 Gly Lys Glu Val Cys Tyr Glu Arg LeuGly Cys Phe Lys Asp Gly Leu 20 25 30 Pro Trp Thr Arg Thr Phe Ser Thr GluLeu Val Gly Leu Pro Trp Ser 35 40 45 Pro Glu Lys Ile Asn Thr Arg Phe LeuLeu Tyr Thr Ile His Asn Pro 50 55 60 Asn Ala Tyr Gln Glu Ile Ser Ala ValAsn Ser Ser Thr Ile Gln Ala 65 70 75 80 Ser Tyr Phe Gly Thr Asp Lys IleThr Arg Ile Asn Ile Ala Gly Trp 85 90 95 Lys Thr Asp Gly Lys Trp Gln ArgAsp Met Cys Asn Val Leu Leu Gln 100 105 110 Leu Glu Asp Ile Asn Cys IleAsn Leu Asp Trp Ile Asn Gly Ser Arg 115 120 125 Glu Tyr Ile His Ala ValAsn Asn Leu Arg Val Val Gly Ala Glu Val 130 135 140 Ala Tyr Phe Ile AspVal Leu Met Lys Lys Phe Glu Tyr Ser Pro Ser 145 150 155 160 Lys Val HisLeu Ile Gly His Ser Leu Gly Ala His Leu Ala Gly Glu 165 170 175 Ala GlySer Arg Ile Pro Gly Leu Gly Arg Ile Thr Gly Leu Asp Pro 180 185 190 AlaGly Pro Phe Phe His Asn Thr Pro Lys Glu Val Arg Leu Asp Pro 195 200 205Ser Asp Ala Asn Phe Val Asp Val Ile His Thr Asn Ala Ala Arg Ile 210 215220 Leu Phe Glu Leu Gly Val Gly Thr Ile Asp Ala Cys Gly His Leu Asp 225230 235 240 Phe Tyr Pro Asn Gly Gly Lys His Met Pro Gly Cys Glu Asp LeuIle 245 250 255 Thr Pro Leu Leu Lys Phe Asn Phe Asn Ala Tyr Lys Lys GluMet Ala 260 265 270 Ser Phe Phe Asp Cys Asn His Ala Arg Ser Tyr Gln PheTyr Ala Glu 275 280 285 Ser Ile Leu Asn Pro Asp Ala Phe Ile Ala Tyr ProCys Arg Ser Tyr 290 295 300 Thr Ser Phe Lys Ala Gly Thr Cys Val Gly CysAla Asp Leu Leu His 305 310 315 320 Arg Ile Asp Lys Ile Gly Ser His ThrSer His Val Phe Leu Thr Leu 325 330 335 Ser Leu Pro Phe Leu Leu Val SerLeu Tyr Leu Gly Trp Arg His Lys 340 345 350 Leu Ser Val Lys Leu Ser GlySer Glu Val Thr Gln Gly Thr Val Phe 355 360 365 Leu Arg Val Gly Gly AlaVal Arg Lys Thr Gly Glu Phe Ala Ile Val 370 375 380 Ser Gly Lys Leu GluPro Gly Met Thr Tyr Thr Lys Leu Ile Asp Ala 385 390 395 400 Asp Val AsnVal Gly Asn Ile Thr Ser Val Gln Phe Ile Trp Lys Lys 405 410 415 His LeuPhe Glu Asp Ser Gln Asn Lys Leu Gly Ala Glu Met Val Ile 420 425 430 AsnThr Ser Gly Lys Tyr Gly Tyr Lys Ser Thr Phe Cys Ser Gln Asp 435 440 445Ile Met Gly Pro Asn Ile Leu Gln Asn Leu Lys Pro Cys 450 455 460 24 308PRT Homo sapiens 24 Met Pro Phe Leu Gln Leu Lys Gly Arg Ala Thr Pro ProSer Trp Arg 1 5 10 15 His Asp Ser Arg Ser Leu Val His Leu Leu Asp GlyLys Glu Gly Val 20 25 30 Trp Asp Thr Thr Gly Tyr Ala Leu Gly Ser Arg GluSer Leu Asn Pro 35 40 45 Asp Met Gly Ile Gly Asp Pro His Gly His Ser ThrVal His Thr Arg 50 55 60 Glu Ala Gly Thr Ala Cys Pro Leu Gln Leu Leu GlyAla Arg Glu Ala 65 70 75 80 Ser Leu Leu Ala Cys Gly Ile Cys Gln Ala SerGly Gln Ile Phe Ile 85 90 95 Thr Gln Thr Leu Gly Ile Lys Gly Tyr Arg ThrVal Val Ala Leu Asp 100 105 110 Lys Val Pro Glu Asp Val Gln Glu Tyr SerTrp Tyr Trp Gly Ala Asn 115 120 125 Asp Ser Ala Gly Asn Met Ile Ile SerHis Lys Pro Pro Ser Ala Gln 130 135 140 Gln Pro Gly Pro Met Tyr Thr GlyArg Glu Arg Val Asn Arg Glu Gly 145 150 155 160 Ser Leu Leu Ile Arg ProThr Ala Leu Asn Asp Thr Gly Asn Tyr Thr 165 170 175 Val Arg Val Val AlaGly Asn Glu Thr Gln Arg Ala Thr Gly Trp Leu 180 185 190 Glu Val Leu AspGly Pro Asp Tyr Val Leu Leu Arg Ser Asn Pro Asp 195 200 205 Asp Phe AsnGly Ile Val Thr Ala Glu Ile Gly Ser Gln Val Glu Met 210 215 220 Glu CysIle Cys Tyr Ser Phe Leu Asp Leu Lys Tyr His Trp Ile His 225 230 235 240Asn Gly Ser Leu Leu Asn Phe Ser Asp Ala Lys Met Asn Leu Ser Ser 245 250255 Leu Ala Trp Glu Gln Met Gly Arg Tyr Arg Cys Thr Val Glu Asn Pro 260265 270 Val Thr Gln Leu Ile Met Tyr Met Asp Val Arg Ile Gln Ala Pro His275 280 285 Glu Cys Ser Ser Ser Pro Pro Gly Ser Cys Phe Ala His Leu ProAla 290 295 300 Ser Met Pro Cys 305 25 457 PRT Homo sapiens 25 Met AspLeu Ser Arg Pro Arg Trp Ser Leu Trp Arg Arg Val Phe Leu 1 5 10 15 MetAla Ser Leu Leu Ala Cys Gly Ile Cys Gln Ala Ser Gly Gln Ile 20 25 30 PheIle Thr Gln Thr Leu Gly Ile Lys Gly Tyr Arg Thr Val Val Ala 35 40 45 LeuAsp Lys Val Pro Glu Asp Val Gln Glu Tyr Ser Trp Tyr Trp Gly 50 55 60 AlaAsn Asp Ser Ala Gly Asn Met Ile Ile Ser His Lys Pro Pro Ser 65 70 75 80Ala Gln Gln Pro Gly Pro Met Tyr Thr Gly Arg Glu Arg Val Asn Arg 85 90 95Glu Gly Ser Leu Leu Ile Arg Pro Thr Ala Leu Asn Asp Thr Gly Asn 100 105110 Tyr Thr Val Arg Val Val Ala Gly Asn Glu Thr Gln Arg Ala Thr Gly 115120 125 Trp Leu Glu Val Leu Glu Leu Gly Ser Asn Leu Gly Ile Ser Val Asn130 135 140 Ala Ser Ser Leu Val Glu Asn Met Asp Ser Val Ala Ala Asp CysLeu 145 150 155 160 Thr Asn Val Thr Asn Ile Thr Trp Tyr Val Asn Asp ValPro Thr Ser 165 170 175 Ser Ser Asp Arg Met Thr Ile Ser Pro Asp Gly LysThr Leu Val Ile 180 185 190 Leu Arg Val Ser Arg Tyr Asp Arg Thr Ile GlnCys Met Ile Glu Ser 195 200 205 Phe Pro Glu Ile Phe Gln Arg Ser Glu ArgIle Ser Leu Thr Val Ala 210 215 220 Tyr Gly Pro Asp Tyr Val Leu Leu ArgSer Asn Pro Asp Asp Phe Asn 225 230 235 240 Gly Ile Val Thr Ala Glu IleGly Ser Gln Val Glu Met Glu Cys Ile 245 250 255 Cys Tyr Ser Phe Leu AspLeu Lys Tyr His Trp Ile His Asn Gly Ser 260 265 270 Leu Leu Asn Phe SerAsp Ala Lys Met Asn Leu Ser Ser Leu Ala Trp 275 280 285 Glu Gln Met GlyArg Tyr Arg Cys Thr Val Glu Asn Pro Val Thr Gln 290 295 300 Leu Ile MetTyr Met Asp Val Arg Ile Gln Ala Pro His Glu Cys Pro 305 310 315 320 LeuPro Ser Gly Ile Leu Pro Val Val His Arg Asp Phe Ser Ile Ser 325 330 335Gly Ser Met Val Met Phe Leu Ile Met Leu Thr Val Leu Gly Gly Val 340 345350 Tyr Ile Cys Gly Val Leu Ile His Ala Leu Ile Asn His Tyr Ser Ile 355360 365 Arg Cys Pro His Cys Ser Gly Thr Arg Val Gly Cys Trp Leu Gly Ala370 375 380 Gly Thr Gln Glu Pro Ala Leu Pro Pro Glu Gly Lys Gln Ser GlnLys 385 390 395 400 Gly Arg Asp Lys Pro Gly Thr Arg Leu Ser Gly Ile IleTrp Gly Arg 405 410 415 Gln Ile Ser Pro Gln Asp Leu Lys Leu Met Gly AlaArg Glu Gly Leu 420 425 430 Glu Ser Ala Met Val Leu Asn Ser Cys Gly ValSer Ser Ser Asn Phe 435 440 445 Pro Ser Leu Cys Val Tyr Lys Gly Tyr 450455 26 704 PRT Homo sapiens 26 Met Leu His Asp Gly Leu Thr Ala Pro AspGly Cys Gly Ile Tyr Ser 1 5 10 15 Leu Thr Gly Arg Glu Val Leu Thr ProPhe Pro Gly Leu Gly Thr Ala 20 25 30 Ala Ala Pro Ala Gln Gly Gly Ala HisLeu Lys Gln Cys Asp Leu Leu 35 40 45 Lys Leu Ser Arg Arg Gln Lys Gln LeuCys Arg Arg Glu Pro Gly Leu 50 55 60 Ala Glu Thr Leu Arg Asp Ala Ala HisLeu Gly Leu Leu Glu Cys Gln 65 70 75 80 Phe Gln Phe Arg His Glu Arg TrpAsn Cys Ser Leu Glu Gly Arg Met 85 90 95 Gly Leu Leu Lys Arg Gly Phe LysGlu Thr Ala Phe Leu Tyr Ala Val 100 105 110 Ser Ser Ala Ala Leu Thr HisThr Leu Ala Arg Ala Cys Ser Ala Gly 115 120 125 Arg Met Glu Arg Cys ThrCys Asp Asp Ser Pro Gly Leu Glu Ser Arg 130 135 140 Gln Ala Trp Gln TrpGly Val Cys Gly Asp Asn Leu Lys Tyr Ser Thr 145 150 155 160 Lys Phe LeuSer Asn Phe Leu Gly Ser Lys Arg Gly Asn Lys Asp Leu 165 170 175 Arg AlaArg Ala Asp Ala His Asn Thr His Val Gly Ile Lys Ala Val 180 185 190 LysSer Gly Leu Arg Thr Thr Cys Lys Cys His Gly Val Ser Gly Ser 195 200 205Cys Ala Val Arg Thr Cys Trp Lys Gln Leu Ser Pro Phe Arg Glu Thr 210 215220 Gly Gln Val Leu Lys Leu Arg Tyr Asp Ser Ala Val Lys Val Ser Ser 225230 235 240 Ala Thr Asn Glu Ala Leu Gly Arg Leu Glu Leu Trp Ala Pro AlaArg 245 250 255 Gln Gly Ser Leu Thr Lys Gly Leu Ala Pro Arg Ser Gly AspLeu Val 260 265 270 Tyr Met Glu Asp Ser Pro Ser Phe Cys Arg Pro Ser LysTyr Ser Pro 275 280 285 Gly Thr Ala Gly Arg Val Cys Ser Arg Glu Ala SerCys Ser Ser Leu 290 295 300 Cys Cys Gly Arg Gly Tyr Asp Thr Gln Ser ArgLeu Val Ala Phe Ser 305 310 315 320 Cys His Cys Gln Val Gln Trp Cys CysTyr Val Glu Cys Gln Gln Cys 325 330 335 Val Gln Glu Glu Leu Val Tyr ThrCys Lys His Ala Met Gly Pro Val 340 345 350 Gly Phe Pro Arg Gln Cys GlnGly Ala Phe Phe Glu Ser Ser Pro Gly 355 360 365 Gln Thr Arg Ala Arg LeuThr Gly Arg Glu Val Leu Thr Pro Phe Pro 370 375 380 Gly Leu Gly Thr AlaAla Ala Pro Ala Gln Gly Gly Ala His Leu Lys 385 390 395 400 Gln Cys AspLeu Leu Lys Leu Ser Arg Arg Gln Lys Gln Leu Cys Arg 405 410 415 Arg GluPro Gly Leu Ala Glu Thr Leu Arg Asp Ala Ala His Leu Gly 420 425 430 LeuLeu Glu Cys Gln Phe Gln Phe Arg His Glu Arg Trp Asn Cys Ser 435 440 445Leu Glu Gly Arg Met Gly Leu Leu Lys Arg Gly Phe Lys Glu Thr Ala 450 455460 Phe Leu Tyr Ala Val Ser Ser Ala Ala Leu Thr His Thr Leu Ala Arg 465470 475 480 Ala Cys Ser Ala Gly Arg Met Glu Arg Cys Thr Cys Asp Asp SerPro 485 490 495 Gly Leu Glu Ser Arg Gln Ala Trp Gln Trp Gly Val Cys GlyAsp Asn 500 505 510 Leu Lys Tyr Ser Thr Lys Phe Leu Ser Asn Phe Leu GlySer Lys Arg 515 520 525 Gly Asn Lys Asp Leu Arg Ala Arg Ala Asp Ala HisAsn Thr His Val 530 535 540 Gly Ile Lys Ala Val Lys Ser Gly Leu Arg ThrThr Cys Lys Cys His 545 550 555 560 Gly Val Ser Gly Ser Cys Ala Val ArgThr Cys Trp Lys Gln Leu Ser 565 570 575 Pro Phe Arg Glu Thr Gly Gln ValLeu Lys Leu Arg Tyr Asp Ser Ala 580 585 590 Val Lys Val Ser Ser Ala ThrAsn Glu Ala Leu Gly Arg Leu Glu Leu 595 600 605 Trp Ala Pro Ala Arg GlnGly Ser Leu Thr Lys Gly Leu Ala Pro Arg 610 615 620 Ser Gly Asp Leu ValTyr Met Glu Asp Ser Pro Ser Phe Cys Arg Pro 625 630 635 640 Ser Lys TyrSer Pro Gly Thr Ala Gly Arg Val Cys Ser Arg Glu Ala 645 650 655 Ser CysSer Ser Leu Cys Cys Gly Arg Gly Tyr Asp Thr Gln Ser Arg 660 665 670 LeuVal Ala Phe Ser Cys His Cys Gln Val Gln Trp Cys Cys Tyr Val 675 680 685Glu Cys Gln Gln Cys Val Gln Glu Glu Leu Val Tyr Thr Cys Lys His 690 695700 27 361 PRT Homo sapiens 27 Met Lys Pro Leu Arg Arg Pro Leu Pro PheIle Cys Pro Ser Pro Pro 1 5 10 15 Ser Pro Arg Leu Thr Cys Leu Pro ProLeu Ala Leu Ser Ser Leu Thr 20 25 30 Gly Arg Glu Val Leu Thr Pro Phe ProGly Leu Gly Thr Ala Ala Ala 35 40 45 Pro Ala Gln Gly Gly Ala His Leu LysGln Cys Asp Leu Leu Lys Leu 50 55 60 Ser Arg Arg Gln Lys Gln Leu Cys ArgArg Glu Pro Gly Leu Ala Glu 65 70 75 80 Thr Leu Arg Asp Ala Ala His LeuGly Leu Leu Glu Cys Gln Phe Gln 85 90 95 Phe Arg His Glu Arg Trp Asn CysSer Leu Glu Gly Arg Met Gly Leu 100 105 110 Leu Lys Arg Gly Phe Lys GluThr Ala Phe Leu Tyr Ala Val Ser Ser 115 120 125 Ala Ala Leu Thr His ThrLeu Ala Arg Ala Cys Ser Ala Gly Arg Met 130 135 140 Glu Arg Cys Thr CysAsp Asp Ser Pro Gly Leu Glu Ser Arg Gln Ala 145 150 155 160 Trp Gln TrpGly Val Cys Gly Asp Asn Leu Lys Tyr Ser Thr Lys Phe 165 170 175 Leu SerAsn Phe Leu Gly Ser Lys Arg Gly Asn Lys Asp Leu Arg Ala 180 185 190 ArgAla Asp Ala His Asn Thr His Val Gly Ile Lys Ala Val Lys Ser 195 200 205Gly Leu Arg Thr Thr Cys Lys Cys His Gly Val Ser Gly Ser Cys Ala 210 215220 Val Arg Thr Cys Trp Lys Gln Leu Ser Pro Phe Arg Glu Thr Gly Gln 225230 235 240 Val Leu Lys Leu Arg Tyr Asp Ser Ala Val Lys Val Ser Ser AlaThr 245 250 255 Asn Glu Ala Leu Gly Arg Leu Glu Leu Trp Ala Pro Ala ArgGln Gly 260 265 270 Ser Leu Thr Lys Gly Leu Ala Pro Arg Ser Gly Asp LeuVal Tyr Met 275 280 285 Glu Asp Ser Pro Ser Phe Cys Arg Pro Ser Lys TyrSer Pro Gly Thr 290 295 300 Ala Gly Arg Val Cys Ser Arg Glu Ala Ser CysSer Ser Leu Cys Cys 305 310 315 320 Gly Arg Gly Tyr Asp Thr Gln Ser ArgLeu Val Ala Phe Ser Cys His 325 330 335 Cys Gln Val Gln Trp Cys Cys TyrVal Glu Cys Gln Gln Cys Val Gln 340 345 350 Glu Glu Leu Val Tyr Thr CysLys His 355 360 28 365 PRT Homo sapiens 28 Met Trp Leu Leu Leu Thr ThrThr Cys Leu Ile Cys Gly Thr Leu Asn 1 5 10 15 Ala Gly Gly Phe Leu AspLeu Glu Asn Glu Val Asn Pro Glu Val Trp 20 25 30 Met Asn Thr Ser Glu IleIle Ile Tyr Asn Gly Tyr Pro Ser Glu Glu 35 40 45 Tyr Glu Val Thr Thr GluAsp Gly Tyr Ile Leu Leu Val Asn Arg Ile 50 55 60 Pro Tyr Gly Arg Thr HisAla Arg Ser Thr Ala Asp Ala Gly Tyr Asp 65 70 75 80 Val Trp Met Gly AsnSer Arg Gly Asn Thr Trp Ser Arg Arg His Lys 85 90 95 Thr Leu Ser Glu ThrAsp Glu Lys Phe Trp Ala Phe Ser Phe Asp Glu 100 105 110 Met Ala Lys TyrAsp Leu Pro Gly Val Ile Asp Phe Ile Val Asn Lys 115 120 125 Thr Gly GlnGlu Lys Leu Tyr Phe Ile Gly His Ser Leu Gly Thr Thr 130 135 140 Ile GlyPhe Val Ala Phe Ser Thr Met Pro Glu Leu Ala Gln Arg Ile 145 150 155 160Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe Lys Tyr Pro Thr 165 170175 Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser Ile Ile Lys Ala 180185 190 Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys Lys Thr Lys Ile195 200 205 Ala Ser Thr Lys Ile Cys Asn Asn Lys Ile Leu Trp Leu Ile CysSer 210 215 220 Glu Phe Met Ser Leu Trp Ala Gly Ser Asn Lys Lys Asn MetAsn Gln 225 230 235 240 Ser Arg Met Asp Val Tyr Met Ser His Ala Pro ThrGly Ser Ser Val 245 250 255 His Asn Ile Leu His Ile Lys Gln Leu Tyr HisSer Asp Glu Phe Arg 260 265 270 Ala Tyr Asp Trp Gly Asn Asp Ala Asp AsnMet Lys His Tyr Asn Gln 275 280 285 Ser His Pro Pro Ile Tyr Asp Leu ThrAla Met Lys Val Pro Thr Ala 290 295 300 Ile Trp Ala Gly Gly His Asp ValLeu Val Thr Pro Gln Asp Val Ala 305 310 315 320 Arg Ile Leu Pro Gln IleLys Ser Leu His Tyr Phe Lys Leu Leu Pro 325 330 335 Asp Trp Asn His PheAsp Phe Val Trp Gly Leu Asp Ala Pro Gln Arg 340 345 350 Met Tyr Ser GluIle Ile Ala Leu Met Lys Ala Tyr Ser 355 360 365 29 397 PRT Homo sapiens29 Met Trp Gln Leu Leu Ala Ala Ala Cys Trp Met Leu Leu Leu Gly Ser 1 510 15 Met Tyr Gly Tyr Asp Lys Lys Gly Asn Asn Ala Asn Pro Glu Ala Asn 2025 30 Met Asn Ile Ser Gln Ile Ile Ser Tyr Trp Gly Tyr Pro Tyr Glu Glu 3540 45 Tyr Asp Val Thr Thr Lys Asp Gly Tyr Ile Leu Gly Ile Tyr Arg Ile 5055 60 Pro His Gly Arg Gly Cys Pro Gly Arg Thr Ala Pro Lys Pro Ala Val 6570 75 80 Tyr Leu Gln His Gly Leu Ile Ala Ser Ala Ser Asn Trp Ile Cys Asn85 90 95 Leu Pro Asn Asn Ser Leu Ala Phe Leu Leu Ala Asp Ser Gly Tyr Asp100 105 110 Val Trp Leu Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Lys HisLeu 115 120 125 Lys Leu Ser Pro Lys Ser Pro Glu Tyr Trp Ala Phe Ser LeuAsp Glu 130 135 140 Met Ala Lys Tyr Asp Leu Pro Ala Thr Ile Asn Phe IleIle Glu Lys 145 150 155 160 Thr Gly Gln Lys Arg Leu Tyr Tyr Val Gly HisSer Gln Gly Thr Thr 165 170 175 Ile Ala Phe Ile Ala Phe Ser Thr Asn ProGlu Leu Ala Lys Lys Ile 180 185 190 Lys Ile Phe Phe Ala Leu Ala Pro ValVal Thr Val Lys Tyr Thr Gln 195 200 205 Ser Pro Met Lys Lys Leu Thr ThrLeu Ser Arg Arg Val Val Lys Val 210 215 220 Leu Phe Gly Asp Lys Met PheHis Pro His Thr Leu Phe Asp Gln Phe 225 230 235 240 Ile Ala Thr Lys ValCys Asn Arg Lys Leu Phe Arg Arg Ile Cys Ser 245 250 255 Asn Phe Leu PheThr Leu Ser Gly Phe Asp Pro Gln Asn Leu Asn Met 260 265 270 Ser Arg LeuAsp Val Tyr Leu Ser His Asn Pro Ala Gly Thr Ser Val 275 280 285 Gln AsnMet Leu His Trp Ala Gln Leu Tyr His Ser Asp Glu Phe Arg 290 295 300 AlaTyr Asp Trp Gly Asn Asp Ala Asp Asn Met Lys His Tyr Asn Gln 305 310 315320 Ser His Pro Pro Ile Tyr Asp Leu Thr Ala Met Lys Val Pro Thr Ala 325330 335 Ile Trp Ala Gly Gly His Asp Val Leu Val Thr Pro Gln Asp Val Ala340 345 350 Arg Ile Leu Pro Gln Ile Lys Ser Leu His Tyr Phe Lys Leu LeuPro 355 360 365 Asp Trp Asn His Phe Asp Phe Val Trp Gly Leu Asp Ala ProGln Arg 370 375 380 Met Tyr Ser Glu Ile Ile Ala Leu Met Lys Ala Tyr Ser385 390 395 30 3705 PRT Homo sapiens 30 Met Ala Lys Arg Leu Cys Ala GlySer Ala Leu Cys Val Arg Gly Pro 1 5 10 15 Arg Gly Pro Ala Pro Leu LeuLeu Val Gly Leu Ala Leu Leu Gly Ala 20 25 30 Ala Arg Ala Arg Glu Glu AlaGly Gly Gly Phe Ser Leu His Pro Pro 35 40 45 Tyr Phe Asn Leu Ala Glu GlyAla Arg Ile Ala Ala Ser Ala Thr Cys 50 55 60 Gly Glu Glu Ala Pro Ala ArgGly Ser Pro Arg Pro Thr Glu Asp Leu 65 70 75 80 Tyr Cys Lys Leu Val GlyGly Pro Val Ala Gly Gly Asp Pro Asn Gln 85 90 95 Thr Ile Arg Gly Gln TyrCys Asp Ile Cys Thr Ala Ala Asn Ser Asn 100 105 110 Lys Ala His Pro AlaSer Asn Ala Ile Asp Gly Thr Glu Arg Trp Trp 115 120 125 Gln Ser Pro ProLeu Ser Arg Gly Leu Glu Tyr Asn Glu Val Asn Val 130 135 140 Thr Leu AspLeu Gly Gln Val Phe His Val Ala Tyr Val Leu Ile Lys 145 150 155 160 PheAla Asn Ser Pro Arg Pro Asp Leu Trp Val Leu Glu Arg Ser Met 165 170 175Asp Phe Gly Arg Thr Tyr Gln Pro Trp Gln Phe Phe Ala Ser Ser Lys 180 185190 Arg Asp Cys Leu Glu Arg Phe Gly Pro Gln Thr Leu Glu Arg Ile Thr 195200 205 Arg Asp Asp Ala Ala Ile Cys Thr Thr Glu Tyr Ser Arg Ile Val Pro210 215 220 Leu Glu Asn Gly Glu Ile Val Val Ser Leu Val Asn Gly Arg ProGly 225 230 235 240 Ala Met Asn Phe Ser Tyr Ser Pro Leu Leu Arg Glu PheThr Lys Ala 245 250 255 Thr Asn Val Arg Leu Arg Phe Leu Arg Thr Asn ThrLeu Leu Gly His 260 265 270 Leu Met Gly Lys Ala Leu Arg Asp Pro Thr ValThr Arg Arg Tyr Tyr 275 280 285 Tyr Ser Ile Lys Asp Ile Ser Ile Gly GlyArg Cys Val Cys His Gly 290 295 300 His Ala Asp Ala Cys Asp Ala Lys AspPro Thr Asp Pro Phe Arg Leu 305 310 315 320 Gln Cys Thr Cys Gln His AsnThr Cys Gly Gly Thr Cys Asp Arg Cys 325 330 335 Cys Pro Gly Phe Asn GlnGln Pro Trp Lys Pro Ala Thr Ala Asn Ser 340 345 350 Ala Asn Glu Cys GlnSer Cys Asn Cys Tyr Gly His Ala Thr Asp Cys 355 360 365 Tyr Tyr Asp ProGlu Val Asp Arg Arg Arg Ala Ser Gln Ser Leu Asp 370 375 380 Gly Thr TyrGln Gly Gly Gly Val Cys Ile Asp Cys Gln His His Thr 385 390 395 400 ThrGly Val Asn Cys Glu Arg Cys Leu Pro Gly Phe Tyr Arg Ser Pro 405 410 415Asn His Pro Leu Asp Ser Pro His Val Cys Arg Arg Cys Asn Cys Glu 420 425430 Ser Asp Phe Thr Asp Gly Thr Cys Glu Asp Leu Thr Gly Arg Cys Tyr 435440 445 Cys Arg Pro Asn Phe Ser Gly Glu Arg Cys Asp Val Cys Ala Glu Gly450 455 460 Phe Thr Gly Phe Pro Ser Cys Tyr Pro Thr Pro Ser Ser Ser AsnAsp 465 470 475 480 Thr Arg Glu Gln Val Leu Pro Ala Gly Gln Ile Val AsnCys Asp Cys 485 490 495 Ser Ala Ala Gly Thr Gln Gly Asn Ala Cys Arg LysAsp Pro Arg Val 500 505 510 Gly Arg Cys Leu Cys Lys Pro Asn Phe Gln GlyThr His Cys Glu Leu 515 520 525 Cys Ala Pro Gly Phe Tyr Gly Pro Gly CysGln Pro Cys Gln Cys Ser 530 535 540 Ser Pro Gly Val Ala Asp Asp Arg CysAsp Pro Asp Thr Gly Gln Cys 545 550 555 560 Arg Cys Arg Val Gly Phe GluGly Ala Thr Cys Asp Arg Cys Ala Pro 565 570 575 Gly Tyr Phe His Phe ProLeu Cys Gln Leu Cys Gly Cys Ser Pro Ala 580 585 590 Gly Thr Leu Pro GluGly Cys Asp Glu Ala Gly Arg Cys Leu Cys Gln 595 600 605 Pro Glu Phe AlaGly Pro His Cys Asp Arg Cys Arg Pro Gly Tyr His 610 615 620 Gly Phe ProAsn Cys Gln Ala Cys Thr Cys Asp Pro Arg Gly Ala Leu 625 630 635 640 AspGln Leu Cys Gly Ala Gly Gly Leu Cys Arg Cys Arg Pro Gly Tyr 645 650 655Thr Gly Thr Ala Cys Gln Glu Cys Ser Pro Gly Phe His Gly Phe Pro 660 665670 Ser Cys Val Pro Cys His Cys Ser Ala Glu Gly Ser Leu His Ala Ala 675680 685 Cys Asp Pro Arg Ser Gly Gln Cys Ser Cys Arg Pro Arg Val Thr Gly690 695 700 Leu Arg Cys Asp Thr Cys Val Pro Gly Ala Tyr Asn Phe Pro TyrCys 705 710 715 720 Glu Ala Gly Ser Cys His Pro Ala Gly Leu Ala Pro ValAsp Pro Ala 725 730 735 Leu Pro Glu Ala Gln Val Pro Cys Met Cys Arg AlaHis Val Glu Gly 740 745 750 Pro Ser Cys Asp Arg Cys Lys Pro Gly Phe TrpGly Leu Ser Pro Ser 755 760 765 Asn Pro Glu Gly Cys Thr Arg Cys Ser CysAsp Leu Arg Gly Thr Leu 770 775 780 Gly Gly Val Ala Glu Cys Gln Pro GlyThr Gly Gln Cys Phe Cys Lys 785 790 795 800 Pro His Val Cys Gly Gln AlaCys Ala Ser Cys Lys Asp Gly Phe Phe 805 810 815 Gly Leu Asp Gln Ala AspTyr Phe Gly Cys Arg Ser Cys Arg Cys Asp 820 825 830 Ile Gly Gly Ala LeuGly Gln Ser Cys Glu Pro Arg Thr Gly Val Cys 835 840 845 Arg Cys Arg ProAsn Thr Gln Gly Pro Thr Cys Ser Glu Pro Ala Arg 850 855 860 Asp His TyrLeu Pro Asp Leu His His Leu Arg Leu Glu Leu Glu Glu 865 870 875 880 AlaAla Thr Pro Glu Gly His Ala Val Arg Phe Gly Phe Asn Pro Leu 885 890 895Glu Phe Glu Asn Phe Ser Trp Arg Gly Tyr Ala Gln Met Ala Pro Val 900 905910 Gln Pro Arg Ile Val Ala Arg Leu Asn Leu Thr Ser Pro Asp Leu Phe 915920 925 Trp Leu Val Phe Arg Tyr Val Asn Arg Gly Ala Met Ser Val Ser Gly930 935 940 Arg Val Ser Val Arg Glu Glu Gly Arg Ser Ala Thr Cys Ala AsnCys 945 950 955 960 Thr Ala Gln Ser Gln Pro Val Ala Phe Pro Pro Ser ThrGlu Pro Ala 965 970 975 Phe Ile Thr Val Pro Gln Arg Gly Phe Gly Glu ProPhe Val Leu Asn 980 985 990 Pro Gly Thr Trp Ala Leu Arg Val Glu Ala GluGly Val Leu Leu Asp 995 1000 1005 Tyr Val Val Leu Leu Pro Ser Ala TyrTyr Glu Ala Ala Leu Leu Gln 1010 1015 1020 Leu Arg Val Thr Glu Ala CysThr Tyr Arg Pro Ser Ala Gln Gln Ser 1025 1030 1035 1040 Gly Asp Asn CysLeu Leu Tyr Thr His Leu Pro Leu Asp Gly Phe Pro 1045 1050 1055 Ser AlaAla Gly Leu Glu Ala Leu Cys Arg Gln Asp Asn Ser Leu Pro 1060 1065 1070Arg Pro Cys Pro Thr Glu Gln Leu Ser Pro Ser His Pro Pro Leu Ile 10751080 1085 Thr Cys Thr Gly Ser Asp Val Asp Val Gln Leu Gln Val Ala ValPro 1090 1095 1100 Gln Pro Gly Arg Tyr Ala Leu Val Val Glu Tyr Ala AsnGlu Asp Ala 1105 1110 1115 1120 Arg Gln Glu Val Gly Val Ala Val His ThrPro Gln Arg Ala Pro Gln 1125 1130 1135 Gln Gly Leu Leu Ser Leu His ProCys Leu Tyr Ser Thr Leu Cys Arg 1140 1145 1150 Gly Thr Ala Arg Asp ThrGln Asp His Leu Ala Val Phe His Leu Asp 1155 1160 1165 Ser Glu Ala SerVal Arg Leu Thr Ala Glu Gln Ala Arg Phe Phe Leu 1170 1175 1180 His GlyVal Thr Leu Val Pro Ile Glu Glu Phe Ser Pro Glu Phe Val 1185 1190 11951200 Glu Pro Arg Val Ser Cys Ile Ser Ser His Gly Ala Phe Gly Pro Asn1205 1210 1215 Ser Ala Ala Cys Leu Pro Ser Arg Phe Pro Lys Pro Pro GlnPro Ile 1220 1225 1230 Ile Leu Arg Asp Cys Gln Val Ile Pro Leu Pro ProGly Leu Pro Leu 1235 1240 1245 Thr His Ala Gln Asp Leu Thr Pro Ala MetSer Pro Ala Gly Pro Arg 1250 1255 1260 Pro Arg Pro Pro Thr Ala Val AspPro Asp Ala Glu Pro Thr Leu Leu 1265 1270 1275 1280 Arg Glu Pro Gln AlaThr Val Val Phe Thr Thr His Val Pro Thr Leu 1285 1290 1295 Gly Arg TyrAla Phe Leu Leu His Gly Tyr Gln Pro Ala His Pro Thr 1300 1305 1310 PhePro Val Glu Val Leu Ile Asn Ala Gly Arg Val Trp Gln Gly His 1315 13201325 Ala Asn Ala Ser Phe Cys Pro His Gly Tyr Gly Cys Arg Thr Leu Val1330 1335 1340 Val Cys Glu Gly Gln Ala Leu Leu Asp Val Thr His Ser GluLeu Thr 1345 1350 1355 1360 Val Thr Val Arg Val Pro Lys Gly Arg Trp LeuTrp Leu Asp Tyr Val 1365 1370 1375 Leu Val Val Pro Glu Asn Val Tyr SerPhe Gly Tyr Leu Arg Glu Glu 1380 1385 1390 Pro Leu Asp Lys Ser Tyr AspPhe Ile Ser His Cys Ala Ala Gln Gly 1395 1400 1405 Tyr His Ile Ser ProSer Ser Ser Ser Leu Phe Cys Arg Asn Ala Ala 1410 1415 1420 Ala Ser LeuSer Leu Phe Tyr Asn Asn Gly Ala Arg Pro Cys Gly Cys 1425 1430 1435 1440His Glu Val Gly Ala Thr Gly Pro Thr Cys Glu Pro Phe Gly Gly Gln 14451450 1455 Cys Pro Cys His Ala His Val Ile Gly Arg Asp Cys Ser Arg CysAla 1460 1465 1470 Thr Gly Tyr Trp Gly Phe Pro Asn Cys Arg Pro Cys AspCys Gly Ala 1475 1480 1485 Arg Leu Cys Asp Glu Leu Thr Gly Gln Cys IleCys Pro Pro Arg Thr 1490 1495 1500 Ile Pro Pro Asp Cys Leu Leu Cys GlnPro Gln Thr Phe Gly Cys His 1505 1510 1515 1520 Pro Leu Val Gly Cys GluGlu Cys Asn Cys Ser Gly Pro Gly Ile Gln 1525 1530 1535 Glu Leu Thr AspPro Thr Cys Asp Thr Asp Ser Gly Gln Cys Lys Cys 1540 1545 1550 Arg ProAsn Val Thr Gly Arg Arg Cys Asp Thr Cys Ser Pro Gly Phe 1555 1560 1565His Gly Tyr Pro Arg Cys Arg Pro Cys Asp Cys His Glu Ala Gly Thr 15701575 1580 Ala Pro Gly Val Cys Asp Pro Leu Thr Gly Gln Cys Tyr Cys LysGlu 1585 1590 1595 1600 Asn Val Gln Gly Pro Lys Cys Asp Gln Cys Ser LeuGly Thr Phe Ser 1605 1610 1615 Leu Asp Ala Ala Asn Pro Lys Gly Cys ThrArg Cys Phe Cys Phe Gly 1620 1625 1630 Ala Thr Glu Arg Cys Arg Ser SerSer Tyr Thr Arg Gln Glu Phe Val 1635 1640 1645 Asp Met Glu Gly Trp ValLeu Leu Ser Thr Asp Arg Gln Val Val Pro 1650 1655 1660 His Glu Arg GlnPro Gly Thr Glu Met Leu Arg Ala Asp Leu Arg His 1665 1670 1675 1680 ValPro Glu Ala Val Pro Glu Ala Phe Pro Glu Leu Tyr Trp Gln Ala 1685 16901695 Pro Pro Ser Tyr Leu Gly Asp Arg Val Ser Ser Tyr Gly Gly Thr Leu1700 1705 1710 Arg Tyr Glu Leu His Ser Glu Thr Gln Arg Gly Asp Val PheVal Pro 1715 1720 1725 Met Glu Ser Arg Pro Asp Val Val Leu Gln Gly AsnGln Met Ser Ile 1730 1735 1740 Thr Phe Leu Glu Pro Ala Tyr Pro Thr ProGly His Val His Arg Gly 1745 1750 1755 1760 Gln Leu Gln Leu Val Glu GlyAsn Phe Arg His Thr Glu Thr Arg Asn 1765 1770 1775 Thr Val Ser Arg GluGlu Leu Met Met Val Leu Ala Ser Leu Glu Gln 1780 1785 1790 Leu Gln IleArg Ala Leu Phe Ser Gln Ile Ser Ser Ala Val Phe Leu 1795 1800 1805 ArgArg Val Ala Leu Glu Val Ala Ser Pro Ala Gly Gln Gly Ala Leu 1810 18151820 Ala Ser Asn Val Glu Leu Cys Leu Cys Pro Ala Ser Tyr Arg Gly Asp1825 1830 1835 1840 Ser Cys Gln Glu Cys Ala Pro Gly Phe Tyr Arg Asp ValLys Gly Leu 1845 1850 1855 Phe Leu Gly Arg Cys Val Pro Cys Gln Cys HisGly His Ser Asp Arg 1860 1865 1870 Cys Leu Pro Gly Ser Gly Val Cys ValAsp Cys Gln His Asn Thr Glu 1875 1880 1885 Gly Ala His Cys Glu Arg CysGln Ala Gly Phe Val Ser Ser Arg Asp 1890 1895 1900 Asp Pro Ser Ala ProCys Val Ser Cys Pro Cys Pro Leu Ser Val Pro 1905 1910 1915 1920 Ser AsnAsn Phe Ala Glu Gly Cys Val Leu Arg Gly Gly Arg Thr Gln 1925 1930 1935Cys Leu Cys Lys Pro Gly Tyr Ala Gly Ala Ser Cys Glu Arg Cys Ala 19401945 1950 Pro Gly Phe Phe Gly Asn Pro Leu Val Leu Gly Ser Ser Cys GlnPro 1955 1960 1965 Cys Asp Cys Ser Gly Asn Gly Asp Pro Asn Leu Leu PheSer Asp Cys 1970 1975 1980 Asp Pro Leu Thr Gly Ala Cys Arg Gly Cys LeuArg His Thr Thr Gly 1985 1990 1995 2000 Pro Arg Cys Glu Ile Cys Ala ProGly Phe Tyr Gly Asn Ala Leu Leu 2005 2010 2015 Pro Gly Asn Cys Thr ArgCys Asp Cys Thr Pro Cys Gly Thr Glu Ala 2020 2025 2030 Cys Asp Pro HisSer Gly His Cys Leu Cys Lys Ala Gly Val Thr Gly 2035 2040 2045 Arg ArgCys Asp Arg Cys Gln Glu Gly His Phe Gly Phe Asp Gly Cys 2050 2055 2060Gly Gly Cys Arg Pro Cys Ala Cys Gly Pro Ala Ala Glu Gly Ser Glu 20652070 2075 2080 Cys His Pro Gln Ser Gly Gln Cys His Cys Arg Pro Gly ThrMet Gly 2085 2090 2095 Pro Gln Cys Arg Glu Cys Ala Pro Gly Tyr Trp GlyLeu Pro Glu Gln 2100 2105 2110 Gly Cys Arg Arg Cys Gln Cys Pro Gly GlyArg Cys Asp Pro His Thr 2115 2120 2125 Gly Arg Cys Asn Cys Pro Pro GlyLeu Ser Gly Glu Arg Cys Asp Thr 2130 2135 2140 Cys Ser Gln Gln His GlnVal Pro Val Pro Gly Gly Pro Val Gly His 2145 2150 2155 2160 Ser Ile HisCys Glu Val Cys Asp His Cys Val Val Leu Leu Leu Asp 2165 2170 2175 AspLeu Glu Arg Ala Gly Ala Leu Leu Pro Ala Ile His Glu Gln Leu 2180 21852190 Arg Gly Ile Asn Ala Ser Ser Met Ala Trp Ala Arg Leu His Arg Leu2195 2200 2205 Asn Ala Ser Ile Ala Asp Leu Gln Ser Gln Leu Arg Ser ProLeu Gly 2210 2215 2220 Pro Arg His Glu Thr Ala Gln Gln Leu Glu Val LeuGlu Gln Gln Ser 2225 2230 2235 2240 Thr Ser Leu Gly Gln Asp Ala Arg ArgLeu Gly Gly Gln Ala Gly Ala 2245 2250 2255 Pro Arg Pro Pro Arg Ala ProGly Gly Phe His Leu Tyr Gln Ala Ser 2260 2265 2270 Gln Leu Leu Ala GlyThr Glu Ala Thr Leu Gly His Ala Lys Thr Leu 2275 2280 2285 Leu Ala AlaIle Arg Ala Val Asp Arg Thr Leu Ser Glu Leu Met Ser 2290 2295 2300 GlnThr Gly His Leu Gly Leu Ala Asn Ala Ser Ala Pro Ser Gly Glu 2305 23102315 2320 Gln Leu Leu Arg Thr Leu Ala Glu Val Glu Arg Leu Leu Trp GluMet 2325 2330 2335 Arg Ala Arg Asp Leu Gly Ala Pro Gln Ala Ala Ala GluAla Glu Leu 2340 2345 2350 Ala Ala Ala Gln Arg Leu Leu Ala Arg Val GlnGlu Gln Leu Ser Ser 2355 2360 2365 Leu Trp Glu Glu Asn Gln Ala Leu AlaThr Gln Thr Arg Asp Arg Leu 2370 2375 2380 Ala Gln His Glu Ala Gly LeuMet Asp Leu Arg Glu Ala Leu Asn Arg 2385 2390 2395 2400 Ala Val Asp AlaThr Arg Glu Ala Gln Glu Leu Asn Ser Arg Asn Gln 2405 2410 2415 Glu ArgLeu Glu Glu Ala Leu Gln Arg Lys Gln Glu Leu Ser Arg Asp 2420 2425 2430Asn Ala Thr Leu Gln Ala Thr Leu His Ala Ala Arg Asp Thr Leu Ala 24352440 2445 Ser Val Phe Arg Leu Leu His Ser Leu Asp Gln Ala Lys Glu GluLeu 2450 2455 2460 Glu Arg Leu Ala Ala Ser Leu Asp Gly Ala Arg Thr ProLeu Leu Gln 2465 2470 2475 2480 Arg Met Gln Thr Phe Ser Pro Ala Gly SerLys Leu Arg Leu Val Glu 2485 2490 2495 Ala Ala Glu Ala His Ala Gln GlnLeu Gly Gln Leu Ala Leu Asn Leu 2500 2505 2510 Ser Ser Ile Ile Leu AspVal Asn Gln Asp Arg Leu Thr Gln Arg Ala 2515 2520 2525 Ile Glu Ala SerAsn Ala Tyr Ser Arg Ile Leu Gln Ala Val Gln Ala 2530 2535 2540 Ala GluAsp Ala Ala Gly Gln Ala Leu Gln Gln Ala Asp His Thr Trp 2545 2550 25552560 Ala Thr Val Val Arg Gln Gly Leu Val Asp Arg Ala Gln Gln Leu Leu2565 2570 2575 Ala Asn Ser Thr Ala Leu Glu Glu Ala Met Leu Gln Glu GlnGln Arg 2580 2585 2590 Leu Gly Leu Val Trp Ala Ala Leu Gln Gly Ala ArgThr Gln Leu Arg 2595 2600 2605 Asp Val Arg Ala Lys Lys Asp Gln Leu GluAla His Ile Gln Ala Ala 2610 2615 2620 Gln Ala Met Leu Ala Met Asp ThrAsp Glu Thr Ser Lys Lys Ile Ala 2625 2630 2635 2640 His Ala Lys Ala ValAla Ala Glu Ala Gln Asp Thr Ala Thr Arg Val 2645 2650 2655 Gln Ser GlnLeu Gln Ala Met Gln Glu Asn Val Glu Arg Trp Gln Gly 2660 2665 2670 GlnTyr Glu Gly Leu Arg Gly Gln Asp Leu Gly Gln Ala Val Leu Asp 2675 26802685 Ala Gly His Ser Val Ser Thr Leu Glu Lys Thr Leu Pro Gln Leu Leu2690 2695 2700 Ala Lys Leu Ser Ile Leu Glu Asn Arg Gly Val His Asn AlaSer Leu 2705 2710 2715 2720 Ala Leu Ser Ala Ser Ile Gly Arg Val Arg GluLeu Ile Ala Gln Ala 2725 2730 2735 Arg Gly Ala Ala Ser Lys Val Lys ValPro Met Lys Phe Asn Gly Arg 2740 2745 2750 Ser Gly Val Gln Leu Arg ThrPro Arg Asp Leu Ala Asp Leu Ala Ala 2755 2760 2765 Tyr Thr Ala Leu LysPhe Tyr Leu Gln Gly Pro Glu Pro Glu Pro Gly 2770 2775 2780 Gln Gly ThrGlu Asp Arg Phe Val Met Tyr Met Gly Ser Arg Gln Ala 2785 2790 2795 2800Thr Gly Asp Tyr Met Gly Val Ser Leu Arg Asp Lys Lys Val His Trp 28052810 2815 Val Tyr Gln Leu Gly Glu Ala Gly Pro Ala Val Leu Ser Ile AspGlu 2820 2825 2830 Asp Ile Gly Glu Gln Phe Ala Ala Val Ser Leu Asp ArgThr Leu Gln 2835 2840 2845 Phe Gly His Met Ser Val Thr Val Glu Arg GlnMet Ile Gln Glu Thr 2850 2855 2860 Lys Gly Asp Thr Val Ala Pro Gly AlaGlu Gly Leu Leu Asn Leu Arg 2865 2870 2875 2880 Pro Asp Asp Phe Val PheTyr Val Gly Gly Tyr Pro Ser Thr Phe Thr 2885 2890 2895 Pro Pro Pro LeuLeu Arg Phe Pro Gly Tyr Arg Gly Cys Ile Glu Met 2900 2905 2910 Asp ThrLeu Asn Glu Glu Val Val Ser Leu Tyr Asn Phe Glu Arg Thr 2915 2920 2925Phe Gln Leu Asp Thr Ala Val Asp Arg Pro Cys Ala Arg Ser Lys Ser 29302935 2940 Thr Gly Asp Pro Trp Leu Thr Asp Gly Ser Tyr Leu Asp Gly ThrGly 2945 2950 2955 2960 Phe Ala Arg Ile Ser Phe Asp Ser Gln Ile Ser ThrThr Lys Arg Phe 2965 2970 2975 Glu Gln Glu Leu Arg Leu Val Ser Tyr SerGly Val Leu Phe Phe Leu 2980 2985 2990 Lys Gln Gln Ser Gln Phe Leu CysLeu Ala Val Gln Glu Gly Ser Leu 2995 3000 3005 Val Leu Leu Tyr Asp PheGly Ala Gly Leu Lys Lys Ala Val Pro Leu 3010 3015 3020 Gln Pro Pro ProPro Leu Thr Ser Ala Ser Lys Ala Ile Gln Val Phe 3025 3030 3035 3040 LeuLeu Gly Gly Ser Arg Lys Arg Val Leu Val Arg Val Glu Arg Ala 3045 30503055 Thr Val Tyr Ser Val Glu Gln Asp Asn Asp Leu Glu Leu Ala Asp Ala3060 3065 3070 Tyr Tyr Leu Gly Gly Val Pro Pro Asp Gln Leu Pro Pro SerLeu Arg 3075 3080 3085 Arg Leu Phe Pro Thr Gly Gly Ser Val Arg Gly CysVal Lys Gly Ile 3090 3095 3100 Lys Ala Leu Gly Lys Tyr Val Asp Leu LysArg Leu Asn Thr Thr Gly 3105 3110 3115 3120 Val Ser Ala Gly Cys Thr AlaAsp Leu Leu Val Gly Arg Ala Met Thr 3125 3130 3135 Phe His Gly His GlyPhe Leu Arg Leu Ala Leu Ser Asn Val Ala Pro 3140 3145 3150 Leu Thr GlyAsn Val Tyr Ser Gly Phe Gly Phe His Ser Ala Gln Asp 3155 3160 3165 SerAla Leu Leu Tyr Tyr Arg Ala Ser Pro Asp Gly Leu Cys Gln Val 3170 31753180 Ser Leu Gln Gln Gly Arg Val Ser Leu Gln Leu Leu Arg Thr Glu Val3185 3190 3195 3200 Lys Thr Gln Ala Gly Phe Ala Asp Gly Ala Pro His TyrVal Ala Phe 3205 3210 3215 Tyr Ser Asn Ala Thr Gly Val Trp Leu Tyr ValAsp Asp Gln Leu Gln 3220 3225 3230 Gln Met Lys Pro His Arg Gly Pro ProPro Glu Leu Gln Pro Gln Pro 3235 3240 3245 Glu Gly Pro Pro Arg Leu LeuLeu Gly Gly Leu Pro Glu Ser Gly Thr 3250 3255 3260 Ile Tyr Asn Phe SerGly Cys Ile Ser Asn Val Phe Val Gln Arg Leu 3265 3270 3275 3280 Leu GlyPro Gln Arg Val Phe Asp Leu Gln Gln Asn Leu Gly Ser Val 3285 3290 3295Asn Val Ser Thr Gly Cys Ala Pro Ala Leu Gln Ala Gln Thr Pro Gly 33003305 3310 Leu Gly Pro Arg Gly Leu Gln Ala Thr Ala Arg Lys Ala Ser ArgArg 3315 3320 3325 Ser Arg Gln Pro Ala Arg His Pro Ala Cys Met Leu ProPro His Leu 3330 3335 3340 Arg Thr Thr Arg Asp Ser Tyr Gln Phe Gly GlySer Leu Ser Ser His 3345 3350 3355 3360 Leu Glu Phe Val Gly Ile Leu AlaArg His Arg Asn Trp Pro Ser Leu 3365 3370 3375 Ser Met His Val Leu ProArg Ser Ser Arg Gly Leu Leu Leu Phe Thr 3380 3385 3390 Ala Arg Leu ArgPro Gly Ser Pro Ser Leu Ala Leu Phe Leu Ser Asn 3395 3400 3405 Gly HisPhe Val Ala Gln Met Glu Gly Leu Gly Thr Arg Leu Arg Ala 3410 3415 3420Gln Ser Arg Gln Arg Ser Arg Pro Gly Arg Trp His Lys Val Ser Val 34253430 3435 3440 Arg Trp Glu Lys Asn Arg Ile Leu Leu Val Thr Asp Gly AlaArg Ala 3445 3450 3455 Trp Ser Gln Glu Gly Pro His Arg Gln His Gln GlyAla Glu His Pro 3460 3465 3470 Gln Pro His Thr Leu Phe Val Gly Gly LeuPro Ala Ser Ser His Ser 3475 3480 3485 Ser Lys Leu Pro Val Thr Val GlyPhe Ser Gly Cys Val Lys Arg Leu 3490 3495 3500 Arg Leu His Gly Arg ProLeu Gly Ala Pro Thr Arg Met Ala Gly Val 3505 3510 3515 3520 Thr Pro CysIle Leu Gly Pro Leu Glu Ala Gly Leu Phe Phe Pro Gly 3525 3530 3535 SerGly Gly Val Ile Thr Leu Asp Leu Pro Gly Ala Thr Leu Pro Asp 3540 35453550 Val Gly Leu Glu Leu Glu Val Arg Pro Leu Ala Val Thr Gly Leu Ile3555 3560 3565 Phe His Leu Gly Gln Ala Arg Thr Pro Pro Tyr Leu Gln LeuGln Val 3570 3575 3580 Thr Glu Lys Gln Val Leu Leu Arg Ala Asp Asp GlyAla Gly Glu Phe 3585 3590 3595 3600 Ser Thr Ser Val Thr Arg Pro Ser ValLeu Cys Asp Gly Gln Trp His 3605 3610 3615 Arg Leu Ala Val Met Lys SerGly Asn Val Leu Arg Leu Glu Val Asp 3620 3625 3630 Ala Gln Ser Asn HisThr Val Gly Pro Leu Leu Ala Ala Ala Ala Gly 3635 3640 3645 Ala Pro AlaPro Leu Tyr Leu Gly Gly Leu Pro Glu Pro Met Ala Val 3650 3655 3660 GlnPro Trp Pro Pro Ala Tyr Cys Gly Cys Met Arg Arg Leu Ala Val 3665 36703675 3680 Asn Arg Ser Pro Val Ala Met Thr Arg Ser Val Glu Val His GlyAla 3685 3690 3695 Val Gly Ala Ser Gly Cys Pro Ala Ala 3700 3705 31 3696PRT Homo sapiens 31 Met Ala Lys Arg Leu Cys Ala Gly Ser Ala Leu Cys ValArg Gly Pro 1 5 10 15 Arg Gly Pro Ala Pro Leu Leu Leu Val Gly Leu AlaLeu Leu Gly Ala 20 25 30 Ala Arg Ala Arg Glu Glu Ala Gly Gly Gly Phe SerLeu His Pro Pro 35 40 45 Tyr Phe Asn Leu Ala Glu Gly Ala Arg Ile Ala AlaSer Ala Thr Cys 50 55 60 Gly Glu Glu Ala Pro Ala Arg Gly Ser Pro Arg ProThr Glu Asp Leu 65 70 75 80 Tyr Cys Lys Leu Val Gly Gly Pro Val Ala GlyGly Asp Pro Asn Gln 85 90 95 Thr Ile Arg Gly Gln Tyr Cys Asp Ile Cys ThrAla Ala Asn Ser Asn 100 105 110 Lys Ala His Pro Ala Ser Asn Ala Ile AspGly Thr Glu Arg Trp Trp 115 120 125 Gln Ser Pro Pro Leu Ser Arg Gly LeuGlu Tyr Asn Glu Val Asn Val 130 135 140 Thr Leu Asp Leu Gly Gln Val PheHis Val Ala Tyr Val Leu Ile Lys 145 150 155 160 Phe Ala Asn Ser Pro ArgPro Asp Leu Trp Val Leu Glu Arg Ser Met 165 170 175 Asp Phe Gly Arg ThrTyr Gln Pro Trp Gln Phe Phe Ala Ser Ser Lys 180 185 190 Arg Asp Cys LeuGlu Arg Phe Gly Pro Gln Thr Leu Glu Arg Ile Thr 195 200 205 Arg Asp AspAla Ala Ile Cys Thr Thr Glu Tyr Ser Arg Ile Val Pro 210 215 220 Leu GluAsn Gly Glu Ile Val Val Ser Leu Val Asn Gly Arg Pro Gly 225 230 235 240Ala Met Asn Phe Ser Tyr Ser Pro Leu Leu Arg Glu Phe Thr Lys Ala 245 250255 Thr Asn Val Arg Leu Arg Phe Leu Arg Thr Asn Thr Leu Leu Gly His 260265 270 Leu Met Gly Lys Ala Leu Arg Asp Pro Thr Val Thr Arg Arg Tyr Tyr275 280 285 Tyr Ser Ile Lys Asp Ile Ser Ile Gly Gly Arg Cys Val Cys HisGly 290 295 300 His Ala Asp Ala Cys Asp Ala Lys Asp Pro Thr Asp Pro PheArg Leu 305 310 315 320 Gln Cys Thr Cys Gln His Asn Thr Cys Gly Gly ThrCys Asp Arg Cys 325 330 335 Cys Pro Gly Phe Asn Gln Gln Pro Trp Lys ProAla Thr Ala Asn Ser 340 345 350 Ala Asn Glu Cys Gln Ser Cys Asn Cys TyrGly His Ala Thr Asp Cys 355 360 365 Tyr Tyr Asp Pro Glu Val Asp Arg ArgArg Ala Ser Gln Ser Leu Asp 370 375 380 Gly Thr Tyr Gln Gly Gly Gly ValCys Ile Asp Cys Gln His His Thr 385 390 395 400 Thr Gly Val Asn Cys GluArg Cys Leu Pro Gly Phe Tyr Arg Ser Pro 405 410 415 Asn His Pro Leu AspSer Pro His Val Cys Arg Arg Cys Asn Cys Glu 420 425 430 Ser Asp Phe ThrAsp Gly Thr Cys Glu Asp Leu Thr Gly Arg Cys Tyr 435 440 445 Cys Arg ProAsn Phe Ser Gly Glu Arg Cys Asp Val Cys Ala Glu Gly 450 455 460 Phe ThrGly Phe Pro Ser Cys Tyr Pro Thr Pro Ser Ser Ser Asn Asp 465 470 475 480Thr Arg Glu Gln Val Leu Pro Ala Gly Gln Ile Val Asn Cys Asp Cys 485 490495 Ser Ala Ala Gly Thr Gln Gly Asn Ala Cys Arg Lys Asp Pro Arg Val 500505 510 Gly Arg Cys Leu Cys Lys Pro Asn Phe Gln Gly Thr His Cys Glu Leu515 520 525 Cys Ala Pro Gly Phe Tyr Gly Pro Gly Cys Gln Pro Cys Gln CysSer 530 535 540 Ser Pro Gly Val Ala Asp Asp Arg Cys Asp Pro Asp Thr GlyGln Cys 545 550 555 560 Arg Cys Arg Val Gly Phe Glu Gly Ala Thr Cys AspArg Cys Ala Pro 565 570 575 Gly Tyr Phe His Phe Pro Leu Cys Gln Leu CysGly Cys Ser Pro Ala 580 585 590 Gly Thr Leu Pro Glu Gly Cys Asp Glu AlaGly Arg Cys Leu Cys Gln 595 600 605 Pro Glu Phe Ala Gly Pro His Cys AspArg Cys Arg Pro Gly Tyr His 610 615 620 Gly Phe Pro Asn Cys Gln Ala CysThr Cys Asp Pro Arg Gly Ala Leu 625 630 635 640 Asp Gln Leu Cys Gly AlaGly Gly Leu Cys Arg Cys Arg Pro Gly Tyr 645 650 655 Thr Gly Thr Ala CysGln Glu Cys Ser Pro Gly Phe His Gly Phe Pro 660 665 670 Ser Cys Val ProCys His Cys Ser Ala Glu Gly Ser Leu His Ala Ala 675 680 685 Cys Asp ProArg Ser Gly Gln Cys Ser Cys Arg Pro Arg Val Thr Gly 690 695 700 Leu ArgCys Asp Thr Cys Val Pro Gly Ala Tyr Asn Phe Pro Tyr Cys 705 710 715 720Glu Ala Gly Ser Cys His Pro Ala Gly Leu Ala Pro Val Asp Pro Ala 725 730735 Leu Pro Glu Ala Gln Val Pro Cys Met Cys Arg Ala His Val Glu Gly 740745 750 Pro Ser Cys Asp Arg Cys Lys Pro Gly Phe Trp Gly Leu Ser Pro Ser755 760 765 Asn Pro Glu Gly Cys Thr Arg Cys Ser Cys Asp Leu Arg Gly ThrLeu 770 775 780 Gly Gly Val Ala Glu Cys Gln Pro Gly Thr Gly Gln Cys PheCys Lys 785 790 795 800 Pro His Val Cys Gly Gln Ala Cys Ala Ser Cys LysAsp Gly Phe Phe 805 810 815 Gly Leu Asp Gln Ala Asp Tyr Phe Gly Cys ArgSer Cys Arg Cys Asp 820 825 830 Ile Gly Gly Ala Leu Gly Gln Ser Cys GluPro Arg Thr Gly Val Cys 835 840 845 Arg Cys Arg Pro Asn Thr Gln Gly ProThr Cys Ser Glu Pro Ala Arg 850 855 860 Asp His Tyr Leu Pro Asp Leu HisHis Leu Arg Leu Glu Leu Glu Glu 865 870 875 880 Ala Ala Thr Pro Glu GlyHis Ala Val Arg Phe Gly Phe Asn Pro Leu 885 890 895 Glu Phe Glu Asn PheSer Trp Arg Gly Tyr Ala Gln Met Ala Pro Val 900 905 910 Gln Pro Arg IleVal Ala Arg Leu Asn Leu Thr Ser Pro Asp Leu Phe 915 920 925 Trp Leu ValPhe Arg Tyr Val Asn Arg Gly Ala Met Ser Val Ser Gly 930 935 940 Arg ValSer Val Arg Glu Glu Gly Arg Ser Ala Thr Cys Ala Asn Cys 945 950 955 960Thr Ala Gln Ser Gln Pro Val Ala Phe Pro Pro Ser Thr Glu Pro Ala 965 970975 Phe Ile Thr Val Pro Gln Arg Gly Phe Gly Glu Pro Phe Val Leu Asn 980985 990 Pro Gly Thr Trp Ala Leu Arg Val Glu Ala Glu Gly Val Leu Leu Asp995 1000 1005 Tyr Val Val Leu Leu Pro Ser Ala Tyr Tyr Glu Ala Ala LeuLeu Gln 1010 1015 1020 Leu Arg Val Thr Glu Ala Cys Thr Tyr Arg Pro SerAla Gln Gln Ser 1025 1030 1035 1040 Gly Asp Asn Cys Leu Leu Tyr Thr HisLeu Pro Leu Asp Gly Phe Pro 1045 1050 1055 Ser Ala Ala Gly Leu Glu AlaLeu Cys Arg Gln Asp Asn Ser Leu Pro 1060 1065 1070 Arg Pro Cys Pro ThrGlu Gln Leu Ser Pro Ser His Pro Pro Leu Ile 1075 1080 1085 Thr Cys ThrGly Ser Asp Val Asp Val Gln Leu Gln Val Ala Val Pro 1090 1095 1100 GlnPro Gly Arg Tyr Ala Leu Val Val Glu Tyr Ala Asn Glu Asp Ala 1105 11101115 1120 Arg Gln Glu Val Gly Val Ala Val His Thr Pro Gln Arg Ala ProGln 1125 1130 1135 Gln Gly Leu Leu Ser Leu His Pro Cys Leu Tyr Ser ThrLeu Cys Arg 1140 1145 1150 Gly Thr Ala Arg Asp Thr Gln Asp His Leu AlaVal Phe His Leu Asp 1155 1160 1165 Ser Glu Ala Ser Val Arg Leu Thr AlaGlu Gln Ala Arg Phe Phe Leu 1170 1175 1180 His Gly Val Thr Leu Val ProIle Glu Glu Phe Ser Pro Glu Phe Val 1185 1190 1195 1200 Glu Pro Arg ValSer Cys Ile Ser Ser His Gly Ala Phe Gly Pro Asn 1205 1210 1215 Ser AlaAla Cys Leu Pro Ser Arg Phe Pro Lys Pro Pro Gln Pro Ile 1220 1225 1230Ile Leu Arg Asp Cys Gln Val Ile Pro Leu Pro Pro Gly Leu Pro Leu 12351240 1245 Thr His Ala Gln Asp Leu Thr Pro Ala Met Ser Pro Ala Gly ProArg 1250 1255 1260 Pro Arg Pro Pro Thr Ala Val Asp Pro Asp Ala Glu ProThr Leu Leu 1265 1270 1275 1280 Arg Glu Pro Gln Ala Thr Val Val Phe ThrThr His Val Pro Thr Leu 1285 1290 1295 Gly Arg Tyr Ala Phe Leu Leu HisGly Tyr Gln Pro Ala His Pro Thr 1300 1305 1310 Phe Pro Val Glu Val LeuIle Asn Ala Gly Arg Val Trp Gln Gly His 1315 1320 1325 Ala Asn Ala SerPhe Cys Pro His Gly Tyr Gly Cys Arg Thr Leu Val 1330 1335 1340 Val CysGlu Gly Gln Ala Leu Leu Asp Val Thr His Ser Glu Leu Thr 1345 1350 13551360 Val Thr Val Arg Val Pro Lys Gly Arg Trp Leu Trp Leu Asp Tyr Val1365 1370 1375 Leu Val Val Pro Glu Asn Val Tyr Ser Phe Gly Tyr Leu ArgGlu Glu 1380 1385 1390 Pro Leu Asp Lys Ser Tyr Asp Phe Ile Ser His CysAla Ala Gln Gly 1395 1400 1405 Tyr His Ile Ser Pro Ser Ser Ser Ser LeuPhe Cys Arg Asn Ala Ala 1410 1415 1420 Ala Ser Leu Ser Leu Phe Tyr AsnAsn Gly Ala Arg Pro Cys Gly Cys 1425 1430 1435 1440 His Glu Val Gly AlaThr Gly Pro Thr Cys Glu Pro Phe Gly Gly Gln 1445 1450 1455 Cys Pro CysHis Ala His Val Ile Gly Arg Asp Cys Ser Arg Cys Ala 1460 1465 1470 ThrGly Tyr Trp Gly Phe Pro Asn Cys Arg Pro Cys Asp Cys Gly Ala 1475 14801485 Arg Leu Cys Asp Glu Leu Thr Gly Gln Cys Ile Cys Pro Pro Arg Thr1490 1495 1500 Ile Pro Pro Asp Cys Leu Leu Cys Gln Pro Gln Thr Phe GlyCys His 1505 1510 1515 1520 Pro Leu Val Gly Cys Glu Glu Cys Asn Cys SerGly Pro Gly Ile Gln 1525 1530 1535 Glu Leu Thr Asp Pro Thr Cys Asp ThrAsp Ser Gly Gln Cys Lys Cys 1540 1545 1550 Arg Pro Asn Val Thr Gly ArgArg Cys Asp Thr Cys Ser Pro Gly Phe 1555 1560 1565 His Gly Tyr Pro ArgCys Arg Pro Cys Asp Cys His Glu Ala Gly Thr 1570 1575 1580 Ala Pro GlyVal Cys Asp Pro Leu Thr Gly Gln Cys Tyr Cys Lys Glu 1585 1590 1595 1600Asn Val Gln Gly Pro Lys Cys Asp Gln Cys Ser Leu Gly Thr Phe Ser 16051610 1615 Leu Asp Ala Ala Asn Pro Lys Gly Cys Thr Arg Cys Phe Cys PheGly 1620 1625 1630 Ala Thr Glu Arg Cys Arg Ser Ser Ser Tyr Thr Arg GlnGlu Phe Val 1635 1640 1645 Asp Met Glu Gly Trp Val Leu Leu Ser Thr AspArg Gln Val Val Pro 1650 1655 1660 His Glu Arg Gln Pro Gly Thr Glu MetLeu Arg Ala Asp Leu Arg His 1665 1670 1675 1680 Val Pro Glu Ala Val ProGlu Ala Phe Pro Glu Leu Tyr Trp Gln Ala 1685 1690 1695 Pro Pro Ser TyrLeu Gly Asp Arg Val Ser Ser Tyr Gly Gly Thr Leu 1700 1705 1710 Arg TyrGlu Leu His Ser Glu Thr Gln Arg Gly Asp Val Phe Val Pro 1715 1720 1725Met Glu Ser Arg Pro Asp Val Val Leu Gln Gly Asn Gln Met Ser Ile 17301735 1740 Thr Phe Leu Glu Pro Ala Tyr Pro Thr Pro Gly His Val His ArgGly 1745 1750 1755 1760 Gln Leu Gln Leu Val Glu Gly Asn Phe Arg His ThrGlu Thr Arg Asn 1765 1770 1775 Thr Val Ser Arg Glu Glu Leu Met Met ValLeu Ala Ser Leu Glu Gln 1780 1785 1790 Leu Gln Ile Arg Ala Leu Phe SerGln Ile Ser Ser Ala Val Phe Leu 1795 1800 1805 Arg Arg Val Ala Leu GluVal Ala Ser Pro Ala Gly Gln Gly Ala Leu 1810 1815 1820 Ala Ser Asn ValGlu Leu Cys Leu Cys Pro Ala Ser Tyr Arg Gly Asp 1825 1830 1835 1840 SerCys Gln Glu Cys Ala Pro Gly Phe Tyr Arg Asp Val Lys Gly Leu 1845 18501855 Phe Leu Gly Arg Cys Val Pro Cys Gln Cys His Gly His Ser Asp Arg1860 1865 1870 Cys Leu Pro Gly Ser Gly Val Cys Val Asp Cys Gln His AsnThr Glu 1875 1880 1885 Gly Ala His Cys Glu Arg Cys Gln Ala Gly Phe ValSer Ser Arg Asp 1890 1895 1900 Asp Pro Ser Ala Pro Cys Val Ser Cys ProCys Pro Leu Ser Val Pro 1905 1910 1915 1920 Ser Asn Asn Phe Ala Glu GlyCys Val Leu Arg Gly Gly Arg Thr Gln 1925 1930 1935 Cys Leu Cys Lys ProGly Tyr Ala Gly Ala Ser Cys Glu Arg Cys Ala 1940 1945 1950 Pro Gly PhePhe Gly Asn Pro Leu Val Leu Gly Ser Ser Cys Gln Pro 1955 1960 1965 CysAsp Cys Ser Gly Asn Gly Asp Pro Asn Leu Leu Phe Ser Asp Cys 1970 19751980 Asp Pro Leu Thr Gly Ala Cys Arg Gly Cys Leu Arg His Thr Thr Gly1985 1990 1995 2000 Pro Arg Cys Glu Ile Cys Ala Pro Gly Phe Tyr Gly AsnAla Leu Leu 2005 2010 2015 Pro Gly Asn Cys Thr Arg Cys Asp Cys Thr ProCys Gly Thr Glu Ala 2020 2025 2030 Cys Asp Pro His Ser Gly His Cys LeuCys Lys Ala Gly Val Thr Gly 2035 2040 2045 Arg Arg Cys Asp Arg Cys GlnGlu Gly His Phe Gly Phe Asp Gly Cys 2050 2055 2060 Gly Gly Cys Arg ProCys Ala Cys Gly Pro Ala Ala Glu Gly Ser Glu 2065 2070 2075 2080 Cys HisPro Gln Ser Gly Gln Cys His Cys Arg Pro Gly Thr Met Gly 2085 2090 2095Pro Gln Cys Arg Glu Cys Ala Pro Gly Tyr Trp Gly Leu Pro Glu Gln 21002105 2110 Gly Cys Arg Arg Cys Gln Cys Pro Gly Gly Arg Cys Asp Pro HisThr 2115 2120 2125 Gly Arg Cys Asn Cys Pro Pro Gly Leu Ser Gly Glu ArgCys Asp Thr 2130 2135 2140 Cys Ser Gln Gln His Gln Val Pro Val Pro GlyGly Pro Val Gly His 2145 2150 2155 2160 Ser Ile His Cys Glu Val Cys AspHis Cys Val Val Leu Leu Leu Asp 2165 2170 2175 Asp Leu Glu Arg Ala GlyAla Leu Leu Pro Ala Ile His Glu Gln Leu 2180 2185 2190 Arg Gly Ile AsnAla Ser Ser Met Ala Trp Ala Arg Leu His Arg Leu 2195 2200 2205 Asn AlaSer Ile Ala Asp Leu Gln Ser Gln Leu Arg Ser Pro Leu Gly 2210 2215 2220Pro Arg His Glu Thr Ala Gln Gln Leu Glu Val Leu Glu Gln Gln Ser 22252230 2235 2240 Thr Ser Leu Gly Gln Asp Ala Arg Arg Leu Gly Gly Gln AlaAla Val 2245 2250 2255 Gly Thr Arg Asp Gln Ala Ser Gln Leu Leu Ala GlyThr Glu Ala Thr 2260 2265 2270 Leu Gly His Ala Lys Thr Leu Leu Ala AlaIle Arg Ala Val Asp Arg 2275 2280 2285 Thr Leu Ser Glu Leu Met Ser GlnThr Gly His Leu Gly Leu Ala Asn 2290 2295 2300 Ala Ser Ala Pro Ser GlyGlu Gln Leu Leu Arg Thr Leu Ala Glu Val 2305 2310 2315 2320 Glu Arg LeuLeu Trp Glu Met Arg Ala Arg Asp Leu Gly Ala Pro Gln 2325 2330 2335 AlaAla Ala Glu Ala Glu Leu Ala Ala Ala Gln Arg Leu Leu Ala Arg 2340 23452350 Val Gln Glu Gln Leu Ser Ser Leu Trp Glu Glu Asn Gln Ala Leu Ala2355 2360 2365 Thr Gln Thr Arg Asp Arg Leu Ala Gln His Glu Ala Gly LeuMet Asp 2370 2375 2380 Leu Arg Glu Ala Leu Asn Arg Ala Val Asp Ala ThrArg Glu Ala Gln 2385 2390 2395 2400 Glu Leu Asn Ser Arg Asn Gln Glu ArgLeu Glu Glu Ala Leu Gln Arg 2405 2410 2415 Lys Gln Glu Leu Ser Arg AspAsn Ala Thr Leu Gln Ala Thr Leu His 2420 2425 2430 Ala Ala Arg Asp ThrLeu Ala Ser Val Phe Arg Leu Leu His Ser Leu 2435 2440 2445 Asp Gln AlaLys Glu Glu Leu Glu Arg Leu Ala Ala Ser Leu Asp Gly 2450 2455 2460 AlaArg Thr Pro Leu Leu Gln Arg Met Gln Thr Phe Ser Pro Ala Gly 2465 24702475 2480 Ser Lys Leu Arg Leu Val Glu Ala Ala Glu Ala His Ala Gln GlnLeu 2485 2490 2495 Gly Gln Leu Ala Leu Asn Leu Ser Ser Ile Ile Leu AspVal Asn Gln 2500 2505 2510 Asp Arg Leu Thr Gln Arg Ala Ile Glu Ala SerAsn Ala Tyr Ser Arg 2515 2520 2525 Ile Leu Gln Ala Val Gln Ala Ala GluAsp Ala Ala Gly Gln Ala Leu 2530 2535 2540 Gln Gln Ala Asp His Thr TrpAla Thr Val Val Arg Gln Gly Leu Val 2545 2550 2555 2560 Asp Arg Ala GlnGln Leu Leu Ala Asn Ser Thr Ala Leu Glu Glu Ala 2565 2570 2575 Met LeuGln Glu Gln Gln Arg Leu Gly Leu Val Trp Ala Ala Leu Gln 2580 2585 2590Gly Ala Arg Thr Gln Leu Arg Asp Val Arg Ala Lys Lys Asp Gln Leu 25952600 2605 Glu Ala His Ile Gln Ala Ala Gln Ala Met Leu Ala Met Asp ThrAsp 2610 2615 2620 Glu Thr Ser Lys Lys Ile Ala His Ala Lys Ala Val AlaAla Glu Ala 2625 2630 2635 2640 Gln Asp Thr Ala Thr Arg Val Gln Ser GlnLeu Gln Ala Met Gln Glu 2645 2650 2655 Asn Val Glu Arg Trp Gln Gly GlnTyr Glu Gly Leu Arg Gly Gln Asp 2660 2665 2670 Leu Gly Gln Ala Val LeuAsp Ala Gly His Ser Val Ser Thr Leu Glu 2675 2680 2685 Lys Thr Leu ProGln Leu Leu Ala Lys Leu Ser Ile Leu Glu Asn Arg 2690 2695 2700 Gly ValHis Asn Ala Ser Leu Ala Leu Ser Ala Ser Ile Gly Arg Val 2705 2710 27152720 Arg Glu Leu Ile Ala Gln Ala Arg Gly Ala Ala Ser Lys Val Lys Val2725 2730 2735 Pro Met Lys Phe Asn Gly Arg Ser Gly Val Gln Leu Arg ThrPro Arg 2740 2745 2750 Asp Leu Ala Asp Leu Ala Ala Tyr Thr Ala Leu LysPhe Tyr Leu Gln 2755 2760 2765 Gly Pro Glu Pro Glu Pro Gly Gln Gly ThrGlu Asp Arg Phe Val Met 2770 2775 2780 Tyr Met Gly Ser Arg Gln Ala ThrGly Asp Tyr Met Gly Val Ser Leu 2785 2790 2795 2800 Arg Asp Lys Lys ValHis Trp Val Tyr Gln Leu Gly Glu Ala Gly Pro 2805 2810 2815 Ala Val LeuSer Ile Asp Glu Asp Ile Gly Glu Gln Phe Ala Ala Val 2820 2825 2830 SerLeu Asp Arg Thr Leu Gln Phe Gly His Met Ser Val Thr Val Glu 2835 28402845 Arg Gln Met Ile Gln Glu Thr Lys Gly Asp Thr Val Ala Pro Gly Ala2850 2855 2860 Glu Gly Leu Leu Asn Leu Arg Pro Asp Asp Phe Val Phe TyrVal Gly 2865 2870 2875 2880 Gly Tyr Pro Ser Thr Phe Thr Pro Pro Pro LeuLeu Arg Phe Pro Gly 2885 2890 2895 Tyr Arg Gly Cys Ile Glu Met Asp ThrLeu Asn Glu Glu Val Val Ser 2900 2905 2910 Leu Tyr Asn Phe Glu Arg ThrPhe Gln Leu Asp Thr Ala Val Asp Arg 2915 2920 2925 Pro Cys Ala Arg SerLys Ser Thr Gly Asp Pro Trp Leu Thr Asp Gly 2930 2935 2940 Ser Tyr LeuAsp Gly Thr Gly Phe Ala Arg Ile Ser Phe Asp Ser Gln 2945 2950 2955 2960Ile Ser Thr Thr Lys Arg Phe Glu Gln Glu Leu Arg Leu Val Ser Tyr 29652970 2975 Ser Gly Val Leu Phe Phe Leu Lys Gln Gln Ser Gln Phe Leu CysLeu 2980 2985 2990 Ala Val Gln Glu Gly Ser Leu Val Leu Leu Tyr Asp PheGly Ala Gly 2995 3000 3005 Leu Lys Lys Ala Val Pro Leu Gln Pro Pro ProPro Leu Thr Ser Ala 3010 3015 3020 Ser Lys Ala Ile Gln Val Phe Leu LeuGly Gly Ser Arg Lys Arg Val 3025 3030 3035 3040 Leu Val Arg Val Glu ArgAla Thr Val Tyr Ser Val Glu Gln Asp Asn 3045 3050 3055 Asp Leu Glu LeuAla Asp Ala Tyr Tyr Leu Gly Gly Val Pro Pro Asp 3060 3065 3070 Gln LeuPro Pro Ser Leu Arg Arg Leu Phe Pro Thr Gly Gly Ser Val 3075 3080 3085Arg Gly Cys Val Lys Gly Ile Lys Ala Leu Gly Lys Tyr Val Asp Leu 30903095 3100 Lys Arg Leu Asn Thr Thr Gly Val Ser Ala Gly Cys Thr Ala AspLeu 3105 3110 3115 3120 Leu Val Gly Arg Ala Met Thr Phe His Gly His GlyPhe Leu Arg Leu 3125 3130 3135 Ala Leu Ser Asn Val Ala Pro Leu Thr GlyAsn Val Tyr Ser Gly Phe 3140 3145 3150 Gly Phe His Ser Ala Gln Asp SerAla Leu Leu Tyr Tyr Arg Ala Ser 3155 3160 3165 Pro Asp Gly Leu Cys GlnVal Ser Leu Gln Gln Gly Arg Val Ser Leu 3170 3175 3180 Gln Leu Leu ArgThr Glu Val Lys Thr Gln Ala Gly Phe Ala Asp Gly 3185 3190 3195 3200 AlaPro His Tyr Val Ala Phe Tyr Ser Asn Ala Thr Gly Val Trp Leu 3205 32103215 Tyr Val Asp Asp Gln Leu Gln Gln Met Lys Pro His Arg Gly Pro Pro3220 3225 3230 Pro Glu Leu Gln Pro Gln Pro Glu Gly Pro Pro Arg Leu LeuLeu Gly 3235 3240 3245 Gly Leu Pro Glu Ser Gly Thr Ile Tyr Asn Phe SerGly Cys Ile Ser 3250 3255 3260 Asn Val Phe Val Gln Arg Leu Leu Gly ProGln Arg Val Phe Asp Leu 3265 3270 3275 3280 Gln Gln Asn Leu Gly Ser ValAsn Val Ser Thr Gly Cys Ala Pro Ala 3285 3290 3295 Leu Gln Ala Gln ThrPro Gly Leu Gly Pro Arg Gly Leu Gln Ala Thr 3300 3305 3310 Ala Arg LysAla Ser Arg Arg Ser Arg Gln Pro Ala Arg His Pro Ala 3315 3320 3325 CysMet Leu Pro Pro His Leu Arg Thr Thr Arg Asp Ser Tyr Gln Phe 3330 33353340 Gly Gly Ser Leu Ser Ser His Leu Glu Phe Val Gly Ile Leu Ala Arg3345 3350 3355 3360 His Arg Asn Trp Pro Ser Leu Ser Met His Val Leu ProArg Ser Ser 3365 3370 3375 Arg Gly Leu Leu Leu Phe Thr Ala Arg Leu ArgPro Gly Ser Pro Ser 3380 3385 3390 Leu Ala Leu Phe Leu Ser Asn Gly HisPhe Val Ala Gln Met Glu Gly 3395 3400 3405 Leu Gly Thr Arg Leu Arg AlaGln Ser Arg Gln Arg Ser Arg Pro Gly 3410 3415 3420 Arg Trp His Lys ValSer Val Arg Trp Glu Lys Asn Arg Ile Leu Leu 3425 3430 3435 3440 Val ThrAsp Gly Ala Arg Ala Trp Ser Gln Glu Gly Pro His Arg Gln 3445 3450 3455His Gln Gly Ala Glu His Pro Gln Pro His Thr Leu Phe Val Gly Gly 34603465 3470 Leu Pro Ala Ser Ser His Ser Ser Lys Leu Pro Val Thr Val GlyPhe 3475 3480 3485 Ser Gly Cys Val Lys Arg Leu Arg Leu His Gly Arg ProLeu Gly Ala 3490 3495 3500 Pro Thr Arg Met Ala Gly Val Thr Pro Cys IleLeu Gly Pro Leu Glu 3505 3510 3515 3520 Ala Gly Leu Phe Phe Pro Gly SerGly Gly Val Ile Thr Leu Asp Leu 3525 3530 3535 Pro Gly Ala Thr Leu ProAsp Val Gly Leu Glu Leu Glu Val Arg Pro 3540 3545 3550 Leu Ala Val ThrGly Leu Ile Phe His Leu Gly Gln Ala Arg Thr Pro 3555 3560 3565 Pro TyrLeu Gln Leu Gln Val Thr Glu Lys Gln Val Leu Leu Arg Ala 3570 3575 3580Asp Asp Gly Ala Gly Glu Phe Ser Thr Ser Val Thr Arg Pro Ser Val 35853590 3595 3600 Leu Cys Asp Gly Gln Trp His Arg Leu Ala Val Met Lys SerGly Asn 3605 3610 3615 Val Leu Arg Leu Glu Val Asp Ala Gln Ser Asn HisThr Val Gly Pro 3620 3625 3630 Leu Leu Ala Ala Ala Ala Gly Ala Pro AlaPro Leu Tyr Leu Gly Gly 3635 3640 3645 Leu Pro Glu Pro Met Ala Val GlnPro Trp Pro Pro Ala Tyr Cys Gly 3650 3655 3660 Cys Met Arg Arg Leu AlaVal Asn Arg Ser Pro Val Ala Met Thr Arg 3665 3670 3675 3680 Ser Val GluVal His Gly Ala Val Gly Ala Ser Gly Cys Pro Ala Ala 3685 3690 3695 32337 PRT Homo sapiens 32 Met Thr Asn Asn Ser Gly Ser Lys Ala Glu Leu ValVal Gly Gly Lys 1 5 10 15 Tyr Lys Leu Val Arg Lys Ile Gly Ser Gly SerPhe Gly Asp Val Tyr 20 25 30 Leu Gly Ile Thr Thr Thr Asn Gly Glu Asp ValAla Val Lys Leu Glu 35 40 45 Ser Gln Lys Val Lys His Pro Gln Leu Leu TyrGlu Ser Lys Leu Tyr 50 55 60 Thr Ile Leu Gln Gly Gly Val Gly Ile Pro HisMet His Trp Tyr Gly 65 70 75 80 Gln Glu Lys Asp Asn Asn Val Leu Val MetAsp Leu Leu Gly Pro Ser 85 90 95 Leu Glu Asp Leu Phe Asn Phe Cys Ser ArgArg Phe Thr Met Lys Thr 100 105 110 Val Leu Met Leu Ala Asp Gln Met IleSer Arg Ile Glu Tyr Val His 115 120 125 Thr Lys Asn Phe Leu His Arg AspIle Lys Pro Asp Asn Phe Leu Met 130 135 140 Gly Thr Gly Arg His Cys AsnLys Leu Phe Leu Ile Asp Phe Gly Leu 145 150 155 160 Ala Lys Lys Tyr ArgAsp Asn Arg Thr Arg Gln His Ile Pro Tyr Arg 165 170 175 Glu Asp Lys HisLeu Ile Gly Thr Val Arg Tyr Ala Ser Ile Asn Ala 180 185 190 His Leu GlyIle Glu Gln Ser Arg Arg Asp Asp Met Glu Ser Leu Gly 195 200 205 Tyr ValPhe Met Tyr Phe Asn Arg Thr Ser Leu Pro Trp Gln Gly Leu 210 215 220 ArgAla Met Thr Lys Lys Gln Lys Tyr Glu Lys Ile Ser Glu Lys Lys 225 230 235240 Met Ser Thr Pro Val Glu Val Leu Cys Lys Gly Phe Pro Ala Glu Phe 245250 255 Ala Met Tyr Leu Asn Tyr Cys Arg Gly Leu Arg Phe Glu Glu Val Pro260 265 270 Asp Tyr Met Tyr Leu Arg Gln Leu Phe Arg Ile Leu Phe Arg ThrLeu 275 280 285 Asn His Gln Tyr Asp Tyr Thr Phe Asp Trp Thr Met Leu LysGln Lys 290 295 300 Ala Ala Gln Gln Ala Ala Ser Ser Ser Gly Gln Gly GlnGln Ala Gln 305 310 315 320 Thr Gln Thr Gly Lys Gln Thr Glu Lys Asn LysAsn Asn Val Lys Asp 325 330 335 Asn 33 888 PRT Homo sapiens 33 Met GluSer Leu Leu Leu Pro Val Leu Leu Leu Leu Ala Ile Leu Trp 1 5 10 15 ThrGln Ala Ala Ala Leu Ile Asn Leu Lys Tyr Ser Val Glu Glu Glu 20 25 30 GlnArg Ala Gly Thr Val Ile Ala Asn Val Ala Lys Asp Ala Arg Glu 35 40 45 AlaGly Phe Ala Leu Asp Pro Arg Gln Ala Ser Ala Phe Arg Val Val 50 55 60 SerAsn Ser Ala Pro His Leu Val Asp Ile Asn Pro Ser Ser Gly Leu 65 70 75 80Leu Val Thr Lys Gln Lys Ile Asp Arg Asp Leu Leu Cys Arg Gln Ser 85 90 95Pro Lys Cys Ile Ile Ser Leu Glu Val Met Ser Ser Ser Met Glu Ile 100 105110 Cys Val Ile Lys Val Glu Ile Lys Asp Leu Asn Asp Asn Ala Pro Ser 115120 125 Phe Pro Ala Ala Gln Ile Glu Leu Glu Ile Ser Glu Ala Ala Ser Pro130 135 140 Gly Thr Arg Ile Pro Leu Asp Ser Ala Tyr Asp Pro Asp Ser GlySer 145 150 155 160 Phe Gly Val Gln Thr Tyr Glu Leu Thr Pro Asn Glu LeuPhe Gly Leu 165 170 175 Glu Ile Lys Thr Arg Gly Asp Gly Ser Arg Phe AlaGlu Leu Val Val 180 185 190 Glu Lys Ser Leu Asp Arg Glu Thr Gln Ser HisTyr Ser Phe Arg Ile 195 200 205 Thr Ala Leu Asp Gly Gly Asp Pro Pro ArgLeu Gly Thr Val Gly Leu 210 215 220 Ser Ile Lys Val Thr Asp Ser Asn AspAsn Asn Pro Val Phe Ser Glu 225 230 235 240 Ser Thr Tyr Ala Val Ser ValPro Glu Asn Ser Pro Pro Asn Thr Pro 245 250 255 Val Ile Arg Leu Asn AlaSer Asp Pro Asp Glu Gly Thr Asn Gly Gln 260 265 270 Val Val Tyr Ser PheTyr Gly Tyr Val Asn Asp Arg Thr Arg Glu Leu 275 280 285 Phe Gln Ile AspPro His Ser Gly Leu Val Thr Val Thr Gly Ala Leu 290 295 300 Asp Tyr GluGlu Gly His Val Tyr Glu Leu Asp Val Gln Ala Lys Asp 305 310 315 320 LeuGly Pro Asn Ser Ile Pro Ala His Cys Lys Val Thr Val Ser Val 325 330 335Leu Asp Thr Asn Asp Asn Pro Pro Val Ile Asn Leu Leu Ser Val Asn 340 345350 Ser Glu Leu Val Glu Val Ser Glu Ser Ala Pro Pro Gly Tyr Val Ile 355360 365 Ala Leu Val Arg Val Ser Asp Arg Asp Ser Gly Leu Asn Gly Arg Val370 375 380 Gln Cys Arg Leu Leu Gly Asn Val Pro Phe Arg Leu Gln Glu TyrGlu 385 390 395 400 Ser Phe Ser Thr Ile Leu Val Asp Gly Arg Leu Asp ArgGlu Gln His 405 410 415 Asp Gln Tyr Asn Leu Thr Ile Gln Ala Arg Asp GlyGly Val Pro Met 420 425 430 Leu Gln Ser Ala Lys Ser Phe Thr Val Leu IleThr Asp Glu Asn Asp 435 440 445 Asn His Pro His Phe Ser Lys Pro Tyr TyrGln Val Ile Val Gln Glu 450 455 460 Asn Asn Thr Pro Gly Ala Tyr Leu LeuSer Val Ser Ala Arg Asp Pro 465 470 475 480 Asp Leu Gly Leu Asn Gly SerVal Ser Tyr Gln Ile Val Pro Ser Gln 485 490 495 Val Arg Asp Met Pro ValPhe Thr Tyr Val Ser Ile Asn Pro Asn Ser 500 505 510 Gly Asp Ile Tyr AlaLeu Arg Ser Phe Asn His Glu Gln Thr Lys Ala 515 520 525 Phe Glu Phe LysVal Leu Ala Lys Asp Gly Gly Leu Pro Ser Leu Gln 530 535 540 Ser Asn AlaThr Val Arg Val Ile Ile Leu Asp Val Asn Asp Asn Thr 545 550 555 560 ProVal Ile Thr Ala Pro Pro Leu Ile Asn Gly Thr Ala Glu Val Tyr 565 570 575Ile Pro Arg Asn Ser Gly Ile Gly Tyr Leu Val Thr Val Val Lys Ala 580 585590 Glu Asp Tyr Asp Glu Gly Glu Asn Gly Arg Val Thr Tyr Asp Met Thr 595600 605 Glu Gly Asp Arg Gly Phe Phe Glu Ile Asp Gln Val Asn Gly Glu Val610 615 620 Arg Thr Thr Arg Thr Phe Gly Glu Ser Ser Lys Ser Ser Tyr GluLeu 625 630 635 640 Ile Val Val Ala His Asp His Gly Lys Thr Ser Leu SerAla Ser Ala 645 650 655 Leu Val Leu Ile Tyr Leu Ser Pro Ala Leu Asp AlaGln Glu Ser Met 660 665 670 Gly Ser Val Asn Leu Ser Leu Ile Phe Ile IleAla Leu Gly Ser Ile 675 680 685 Ala Gly Ile Leu Phe Val Thr Met Ile PheVal Ala Ile Lys Cys Lys 690 695 700 Arg Asp Asn Lys Glu Ile Arg Thr TyrAsn Cys Ser Asn Cys Leu Thr 705 710 715 720 Ile Thr Cys Leu Leu Gly CysPhe Ile Lys Gly Gln Asn Ser Lys Cys 725 730 735 Leu His Cys Ile Ser ValSer Pro Ile Ser Glu Glu Gln Asp Lys Lys 740 745 750 Thr Glu Glu Lys ValSer Leu Arg Gly Lys Arg Ile Ala Glu Tyr Ser 755 760 765 Tyr Gly His GlnLys Lys Ser Ser Lys Lys Lys Lys Ile Ser Lys Asn 770 775 780 Asp Ile ArgLeu Val Pro Arg Asp Val Glu Glu Thr Asp Lys Met Asn 785 790 795 800 ValVal Ser Cys Ser Ser Leu Thr Ser Ser Leu Asn Tyr Phe Asp Tyr 805 810 815His Gln Gln Thr Leu Pro Leu Gly Cys Arg Arg Ser Glu Ser Thr Phe 820 825830 Leu Asn Val Glu Asn Gln Asn Thr Arg Asn Thr Ser Ala Asn His Ile 835840 845 Tyr His His Ser Phe Asn Ser Gln Gly Pro Gln Gln Pro Asp Leu Ile850 855 860 Ile Asn Gly Val Pro Leu Pro Glu Val Ser Ala Ala Lys Trp LeuCys 865 870 875 880 Glu Val Leu Pro Gly Leu Leu Leu 885 34 855 PRT Homosapiens 34 Met Glu Ser Leu Leu Leu Pro Val Leu Leu Leu Leu Ala Ile LeuTrp 1 5 10 15 Thr Gln Ala Ala Ala Leu Ile Asn Leu Lys Tyr Ser Val GluGlu Glu 20 25 30 Gln Arg Ala Gly Thr Val Ile Ala Asn Val Ala Lys Asp AlaArg Glu 35 40 45 Ala Gly Phe Ala Leu Asp Pro Arg Gln Ala Ser Ala Phe ArgVal Val 50 55 60 Ser Asn Ser Ala Pro His Leu Val Asp Ile Asn Pro Ser SerGly Leu 65 70 75 80 Leu Val Thr Lys Gln Lys Ile Asp Arg Asp Leu Leu CysArg Gln Ser 85 90 95 Pro Lys Cys Ile Ile Ser Leu Glu Val Met Ser Ser SerMet Glu Ile 100 105 110 Cys Val Ile Lys Val Glu Ile Lys Asp Leu Asn AspAsn Ala Pro Ser 115 120 125 Phe Pro Ala Ala Gln Ile Glu Leu Glu Ile SerGlu Ala Ala Ser Pro 130 135 140 Gly Thr Arg Ile Pro Leu Asp Ser Ala TyrAsp Pro Asp Ser Gly Ser 145 150 155 160 Phe Gly Val Gln Thr Tyr Glu LeuThr Pro Asn Glu Leu Phe Gly Leu 165 170 175 Glu Ile Lys Thr Arg Gly AspGly Ser Arg Phe Ala Glu Leu Val Val 180 185 190 Glu Lys Ser Leu Asp ArgGlu Thr Gln Ser His Tyr Ser Phe Arg Ile 195 200 205 Thr Ala Leu Asp GlyGly Asp Pro Pro Arg Leu Gly Thr Val Gly Leu 210 215 220 Ser Ile Lys ValThr Asp Ser Asn Asp Asn Asn Pro Val Phe Ser Glu 225 230 235 240 Ser ThrTyr Ala Val Ser Val Pro Glu Asn Ser Pro Pro Asn Thr Pro 245 250 255 ValIle Arg Leu Asn Ala Ser Asp Pro Asp Glu Gly Thr Asn Gly Gln 260 265 270Val Val Tyr Ser Phe Tyr Gly Tyr Val Asn Asp Arg Thr Arg Glu Leu 275 280285 Phe Gln Ile Asp Pro His Ser Gly Leu Val Thr Val Thr Gly Ala Leu 290295 300 Asp Tyr Glu Glu Gly His Val Tyr Glu Leu Asp Val Gln Ala Lys Asp305 310 315 320 Leu Gly Pro Asn Ser Ile Pro Ala His Cys Lys Val Thr ValSer Val 325 330 335 Leu Asp Thr Asn Asp Asn Pro Pro Val Ile Asn Leu LeuSer Val Asn 340 345 350 Ser Glu Leu Val Glu Val Ser Glu Ser Ala Pro ProGly Tyr Val Ile 355 360 365 Ala Leu Val Arg Val Ser Asp Arg Asp Ser GlyLeu Asn Gly Arg Val 370 375 380 Gln Cys Arg Leu Leu Gly Asn Val Pro PheArg Leu Gln Glu Tyr Glu 385 390 395 400 Ser Phe Ser Thr Ile Leu Val AspGly Arg Leu Asp Arg Glu Gln His 405 410 415 Asp Gln Tyr Asn Leu Thr IleGln Ala Arg Asp Gly Gly Val Pro Met 420 425 430 Leu Gln Ser Ala Lys SerPhe Thr Val Leu Ile Thr Asp Glu Asn Asp 435 440 445 Asn His Pro His PheSer Lys Pro Tyr Tyr Gln Val Ile Val Gln Glu 450 455 460 Asn Asn Thr ProGly Ala Tyr Leu Leu Ser Val Ser Ala Arg Asp Pro 465 470 475 480 Asp LeuGly Leu Asn Gly Ser Val Ser Tyr Gln Ile Val Pro Ser Gln 485 490 495 ValArg Asp Met Pro Val Phe Thr Tyr Val Ser Ile Asn Pro Asn Ser 500 505 510Gly Asp Ile Tyr Ala Leu Arg Ser Phe Asn His Glu Gln Thr Lys Ala 515 520525 Phe Glu Phe Lys Val Leu Ala Lys Asp Gly Gly Leu Pro Ser Leu Gln 530535 540 Ser Asn Ala Thr Val Arg Val Ile Ile Leu Asp Val Asn Asp Asn Thr545 550 555 560 Pro Val Ile Thr Ala Pro Pro Leu Ile Asn Gly Thr Ala GluVal Tyr 565 570 575 Ile Pro Arg Asn Ser Gly Ile Gly Tyr Leu Val Thr ValVal Lys Ala 580 585 590 Glu Asp Tyr Asp Glu Gly Glu Asn Gly Arg Val ThrTyr Asp Met Thr 595 600 605 Glu Gly Asp Arg Gly Phe Phe Glu Ile Asp GlnVal Asn Gly Glu Val 610 615 620 Arg Thr Thr Arg Thr Phe Gly Glu Ser SerLys Ser Ser Tyr Glu Leu 625 630 635 640 Ile Val Val Ala His Asp His GlyLys Thr Ser Leu Ser Ala Ser Ala 645 650 655 Leu Val Leu Ile Tyr Leu SerPro Ala Leu Asp Ala Gln Glu Ser Met 660 665 670 Gly Ser Val Asn Leu SerLeu Ile Phe Ile Ile Ala Leu Gly Ser Ile 675 680 685 Ala Gly Ile Leu PheVal Thr Met Ile Phe Val Ala Ile Lys Cys Lys 690 695 700 Arg Asp Asn LysGlu Ile Arg Thr Tyr Asn Cys Arg Ile Ala Glu Tyr 705 710 715 720 Ser TyrGly His Gln Lys Lys Ser Ser Lys Lys Lys Lys Ile Ser Lys 725 730 735 AsnAsp Ile Arg Leu Val Pro Arg Asp Val Glu Glu Thr Asp Lys Met 740 745 750Asn Val Val Ser Cys Ser Ser Leu Thr Ser Ser Leu Asn Tyr Phe Asp 755 760765 Tyr His Gln Gln Thr Leu Pro Leu Gly Cys Arg Arg Ser Glu Ser Thr 770775 780 Phe Leu Asn Val Glu Asn Gln Asn Thr Arg Asn Thr Ser Ala Asn His785 790 795 800 Ile Tyr His His Ser Phe Asn Ser Gln Gly Pro Gln Gln ProAsp Leu 805 810 815 Ile Ile Asn Gly Val Pro Leu Pro Glu Thr Glu Asn TyrSer Phe Asp 820 825 830 Ser Asn Tyr Val Asn Ser Arg Ala His Leu Ile LysArg Tyr Val Gly 835 840 845 Leu Leu Ala Tyr Cys Cys Asn 850 855 35 329PRT Homo sapiens 35 Met Val Thr Lys Ala Phe Val Leu Leu Ala Ile Phe AlaGlu Ala Ser 1 5 10 15 Ala Lys Ser Cys Ala Pro Asn Lys Ala Asp Val IleLeu Val Phe Cys 20 25 30 Tyr Pro Lys Thr Ile Ile Thr Lys Ile Pro Glu CysPro Tyr Gly Trp 35 40 45 Glu Val His Gln Leu Ala Leu Gly Gly Leu Cys TyrAsn Gly Val His 50 55 60 Glu Gly Gly Tyr Tyr Gln Phe Val Ile Pro Asp LeuSer Pro Lys Asn 65 70 75 80 Lys Ser Tyr Cys Gly Thr Gln Ser Glu Tyr LysPro Pro Ile Tyr His 85 90 95 Phe Tyr Ser His Ile Val Ser Asn Asp Thr ThrVal Ile Val Lys Asn 100 105 110 Gln Pro Val Asn Tyr Ser Phe Ser Cys ThrTyr His Ser Thr Tyr Leu 115 120 125 Val Asn Gln Ala Ala Phe Asp Gln ArgVal Ala Thr Val His Val Lys 130 135 140 Asn Gly Ser Met Gly Thr Phe GluSer Gln Leu Ser Leu Asn Phe Tyr 145 150 155 160 Thr Asn Ala Lys Phe SerIle Lys Lys Glu Ala Pro Phe Val Leu Glu 165 170 175 Ala Ser Glu Ile GlySer Asp Leu Phe Ala Gly Val Glu Ala Lys Gly 180 185 190 Leu Ser Ile ArgPhe Lys Val Val Leu Asn Ser Cys Trp Ala Thr Pro 195 200 205 Ser Ala AspPhe Met Tyr Pro Leu Gln Trp Gln Leu Ile Asn Lys Gly 210 215 220 Cys ProThr Asp Glu Thr Val Leu Val His Glu Asn Gly Arg Asp His 225 230 235 240Arg Ala Thr Phe Gln Phe Asn Ala Phe Arg Phe Gln Asn Ile Pro Lys 245 250255 Leu Ser Lys Val Trp Leu His Cys Glu Thr Phe Ile Cys Asp Ser Glu 260265 270 Lys Leu Ser Cys Pro Val Thr Cys Asp Lys Arg Lys Arg Leu Leu Arg275 280 285 Asp Gln Thr Gly Gly Val Leu Val Val Glu Leu Ser Leu Arg SerArg 290 295 300 Gly Phe Ser Ser Leu Tyr Ser Phe Ser Asp Val Leu His HisLeu Ile 305 310 315 320 Met Met Leu Gly Ile Cys Ala Val Leu 325 36 232PRT Homo sapiens 36 Met Leu Tyr Thr Arg Lys Asn Leu Thr Cys Ala Gln ThrIle Asn Ser 1 5 10 15 Ser Ala Phe Gly Asn Leu Asn Val Thr Lys Lys ThrThr Phe Ile Val 20 25 30 His Gly Phe Arg Pro Thr Gly Ser Pro Pro Val TrpMet Asp Asp Leu 35 40 45 Val Lys Gly Leu Leu Ser Val Glu Asp Met Asn ValVal Val Val Asp 50 55 60 Trp Asn Arg Gly Ala Thr Thr Leu Ile Tyr Thr HisAla Ser Ser Lys 65 70 75 80 Thr Arg Lys Val Ala Met Val Leu Lys Glu PheIle Asp Gln Met Leu 85 90 95 Ala Glu Gly Ala Ser Leu Asp Asp Ile Tyr MetIle Gly Val Ser Leu 100 105 110 Gly Ala His Ile Ser Gly Phe Val Gly GluMet Tyr Asp Gly Trp Leu 115 120 125 Gly Arg Ile Thr Gly Leu Asp Pro AlaGly Pro Leu Phe Asn Gly Lys 130 135 140 Pro His Gln Asp Arg Leu Asp ProSer Asp Ala Gln Phe Val Asp Val 145 150 155 160 Ile His Ser Asp Thr AspGly Asn Ala Pro Phe Leu Val Ala Leu Gly 165 170 175 Tyr Lys Glu Pro LeuGly Asn Ile Asp Phe Tyr Pro Asn Gly Gly Leu 180 185 190 Asp Gln Pro GlyCys Pro Lys Thr Ile Leu Gly Gly Asn Val Lys Glu 195 200 205 Met Ile GlnAla Ser Tyr Ile Phe Phe Leu Lys Asn Asp Ser Met Asp 210 215 220 Leu SerSer Pro Lys Glu Val Glu 225 230 37 452 PRT Homo sapiens 37 Met Leu ArgPhe Tyr Leu Phe Ile Ser Leu Leu Cys Leu Ser Arg Ser 1 5 10 15 Asp AlaGlu Glu Thr Cys Pro Ser Phe Thr Arg Leu Ser Phe His Ser 20 25 30 Ala ValVal Gly Thr Gly Leu Asn Val Arg Leu Met Leu Tyr Thr Arg 35 40 45 Lys AsnLeu Thr Cys Ala Gln Thr Ile Asn Ser Ser Ala Phe Gly Asn 50 55 60 Leu AsnVal Thr Lys Lys Thr Thr Phe Ile Val His Gly Phe Arg Pro 65 70 75 80 ThrGly Ser Pro Pro Val Trp Met Asp Asp Leu Val Lys Gly Leu Leu 85 90 95 SerVal Glu Asp Met Asn Val Val Val Val Asp Trp Asn Arg Gly Ala 100 105 110Thr Thr Leu Ile Tyr Thr His Ala Ser Ser Lys Thr Arg Lys Val Ala 115 120125 Met Val Leu Lys Glu Phe Ile Asp Gln Met Leu Ala Glu Gly Ala Ser 130135 140 Leu Asp Asp Ile Tyr Met Ile Gly Val Ser Leu Gly Ala His Ile Ser145 150 155 160 Gly Phe Val Gly Glu Met Tyr Asp Gly Trp Leu Gly Arg IleThr Gly 165 170 175 Leu Asp Pro Ala Gly Pro Leu Phe Asn Gly Lys Pro HisGln Asp Arg 180 185 190 Leu Asp Pro Ser Asp Ala Gln Phe Val Asp Val IleHis Ser Asp Thr 195 200 205 Asp Ala Leu Gly Tyr Lys Glu Pro Leu Gly AsnIle Asp Phe Tyr Pro 210 215 220 Asn Gly Gly Leu Asp Gln Pro Gly Cys ProLys Thr Ile Leu Gly Gly 225 230 235 240 Phe Gln Tyr Phe Lys Cys Asp HisGln Arg Ser Val Tyr Leu Tyr Leu 245 250 255 Ser Ser Leu Arg Glu Ser CysThr Ile Thr Ala Tyr Pro Cys Asp Ser 260 265 270 Tyr Gln Asp Tyr Arg AsnGly Lys Cys Val Ser Cys Gly Thr Ser Gln 275 280 285 Lys Glu Ser Cys ProLeu Leu Gly Tyr Tyr Ala Asp Asn Trp Lys Asp 290 295 300 His Leu Arg GlyLys Asp Pro Pro Met Thr Lys Ala Phe Phe Asp Thr 305 310 315 320 Ala GluGlu Ser Pro Phe Cys Met Tyr His Tyr Phe Val Asp Ile Ile 325 330 335 ThrTrp Asp Lys Asn Val Arg Arg Gly Asp Ile Thr Ile Lys Leu Arg 340 345 350Asp Lys Ala Gly Asn Thr His Arg Ser Lys Ile Ile Ser Asn Glu Pro 355 360365 Thr Thr Phe Gln Lys Tyr His Gln Val Ser Leu Leu Ala Arg Phe Asn 370375 380 Gln Asp Leu Asp Lys Val Ala Ala Ile Ser Leu Met Phe Ser Thr Gly385 390 395 400 Ser Leu Ile Gly Pro Arg Tyr Lys Leu Arg Ile Leu Arg MetLys Leu 405 410 415 Arg Ser Leu Ala His Pro Glu Arg Pro Gln Leu Cys ArgTyr Asp Leu 420 425 430 Val Leu Met Glu Asn Val Glu Thr Val Phe Gln ProIle Leu Cys Pro 435 440 445 Glu Leu Gln Leu 450 38 450 PRT Homo sapiens38 Met Gly Leu Arg Ser His His Leu Ser Leu Gly Leu Leu Leu Leu Phe 1 510 15 Leu Leu Pro Ala Glu Cys Leu Gly Ala Glu Gly Arg Leu Ala Leu Lys 2025 30 Leu Phe Arg Asp Leu Phe Ala Asn Tyr Thr Ser Ala Leu Arg Pro Val 3540 45 Ala Asp Thr Asp Gln Thr Leu Asn Val Thr Leu Glu Val Thr Leu Ser 5055 60 Gln Ile Ile Asp Met Asp Glu Arg Asn Gln Val Leu Thr Leu Tyr Leu 6570 75 80 Trp Ile Arg Gln Glu Trp Thr Asp Ala Tyr Leu Arg Trp Asp Pro Asn85 90 95 Ala Tyr Gly Gly Leu Asp Ala Ile Arg Ile Pro Ser Ser Leu Val Trp100 105 110 Arg Pro Asp Ile Val Leu Tyr Asn Lys Ala Asp Ala Gln Pro ProGly 115 120 125 Ser Ala Ser Thr Asn Val Val Leu Arg His Asp Gly Ala ValArg Trp 130 135 140 Asp Ala Pro Ala Ile Thr Arg Ser Ser Cys Arg Val AspVal Ala Ala 145 150 155 160 Phe Pro Phe Asp Ala Gln His Cys Gly Leu ThrPhe Gly Ser Trp Thr 165 170 175 His Gly Gly His Gln Leu Asp Val Arg ProArg Gly Ala Ala Ala Ser 180 185 190 Leu Ala Asp Phe Val Glu Asn Val GluTrp Arg Val Leu Gly Met Pro 195 200 205 Ala Arg Arg Arg Val Leu Thr TyrGly Cys Cys Ser Glu Pro Tyr Pro 210 215 220 Asp Val Thr Phe Thr Leu LeuLeu Arg Arg Arg Ala Ala Ala Tyr Val 225 230 235 240 Cys Asn Leu Leu LeuPro Cys Val Leu Ile Ser Leu Leu Ala Pro Leu 245 250 255 Ala Phe His LeuPro Ala Asp Ser Gly Glu Lys Val Ser Leu Gly Val 260 265 270 Thr Val LeuLeu Ala Leu Thr Val Phe Gln Leu Leu Leu Ala Glu Ser 275 280 285 Met ProPro Ala Glu Ser Val Pro Leu Ile Gly Lys Tyr Tyr Met Ala 290 295 300 ThrMet Thr Met Val Thr Phe Ser Thr Ala Leu Thr Ile Leu Ile Met 305 310 315320 Asn Leu His Tyr Cys Gly Pro Ser Val Arg Pro Val Pro Ala Trp Ala 325330 335 Arg Ala Leu Leu Leu Gly His Leu Ala Arg Gly Leu Cys Val Arg Glu340 345 350 Arg Gly Glu Pro Cys Gly Gln Ser Arg Pro Pro Glu Leu Ser ProSer 355 360 365 Pro Gln Ser Pro Glu Gly Gly Ala Gly Pro Pro Ala Gly ProCys His 370 375 380 Glu Pro Arg Cys Leu Cys Arg Gln Glu Ala Leu Leu HisHis Val Ala 385 390 395 400 Thr Ile Ala Asn Thr Phe Arg Ser His Arg AlaAla Gln Arg Cys His 405 410 415 Glu Asp Trp Lys Arg Leu Ala Arg Val MetAsp Arg Phe Phe Leu Ala 420 425 430 Ile Phe Phe Ser Met Ala Leu Val MetSer Leu Leu Val Leu Val Gln 435 440 445 Ala Leu 450 39 255 PRT Homosapiens 39 Met Val Lys Gly Glu Lys Gly Pro Lys Gly Lys Lys Ile Thr LeuLys 1 5 10 15 Val Ala Arg Asn Cys Ile Lys Ile Thr Phe Asp Gly Lys LysArg Leu 20 25 30 Asp Leu Ser Lys Met Gly Ile Thr Thr Phe Pro Lys Cys IleLeu Arg 35 40 45 Leu Ser Asp Met Asp Glu Leu Asp Leu Ser Arg Asn Leu IleArg Lys 50 55 60 Ile Pro Asp Ser Ile Ser Lys Phe Gln Asn Leu Arg Trp LeuAsp Leu 65 70 75 80 His Ser Asn Tyr Ile Asp Lys Leu Pro Glu Ser Ile GlyGln Met Thr 85 90 95 Ser Leu Leu Tyr Leu Asn Val Ser Asn Asn Arg Leu ThrSer Asn Gly 100 105 110 Leu Pro Val Glu Leu Lys Gln Leu Lys Asn Ile ArgAla Val Asn Leu 115 120 125 Gly Leu Asn His Leu Asp Ser Val Pro Thr ThrLeu Gly Ala Leu Lys 130 135 140 Glu Leu His Glu Val Gly Leu His Asp AsnLeu Leu Asn Asn Ile Pro 145 150 155 160 Val Ser Ile Ser Lys Leu Pro LysLeu Lys Lys Leu Asn Ile Lys Arg 165 170 175 Asn Pro Phe Pro Lys Pro GlyGlu Ser Glu Ile Phe Ile Asp Ser Ile 180 185 190 Arg Arg Leu Glu Asn LeuTyr Val Val Glu Glu Lys Asp Leu Cys Ala 195 200 205 Ala Cys Leu Arg LysCys Gln Asn Ala Arg Asp Asn Leu Asn Arg Ile 210 215 220 Lys Asn Met AlaThr Thr Thr Pro Arg Lys Thr Ile Phe Pro Asn Leu 225 230 235 240 Ile SerPro Asn Ser Met Ala Lys Asp Ser Trp Glu Asp Trp Arg 245 250 255 40 214PRT Homo sapiens 40 Met Gln Ala Gly Thr Gln Ser Thr His Glu Ser Leu LysPro Gln Arg 1 5 10 15 Val Gln Phe Gln Ser Arg Asn Phe His Asn Ile LeuGln Trp Gln Pro 20 25 30 Gly Arg Ala Leu Thr Gly Asn Ser Ser Val Tyr PheVal Gln Tyr Lys 35 40 45 Ile Tyr Gly Gln Arg Gln Trp Lys Asn Lys Glu AspCys Trp Gly Thr 50 55 60 Gln Glu Leu Ser Cys Asp Leu Thr Ser Glu Thr SerAsp Ile Gln Glu 65 70 75 80 Pro Tyr Tyr Gly Arg Val Arg Ala Ala Ser AlaGly Ser Tyr Ser Glu 85 90 95 Trp Ser Met Thr Pro Arg Phe Thr Pro Trp TrpGlu Thr Lys Ile Asp 100 105 110 Pro Pro Val Met Asn Ile Thr Gln Val AsnGly Ser Leu Leu Val Ile 115 120 125 Leu His Ala Pro Asn Leu Pro Tyr ArgTyr Gln Lys Glu Lys Asn Val 130 135 140 Ser Ile Glu Asp Tyr Tyr Glu LeuLeu Tyr Arg Val Phe Ile Ile Asn 145 150 155 160 Asn Ser Leu Glu Lys GluGln Lys Val Tyr Glu Gly Ala His Arg Ala 165 170 175 Val Glu Ile Glu AlaLeu Thr Pro His Ser Ser Tyr Cys Val Val Ala 180 185 190 Glu Ile Tyr GlnPro Met Leu Asp Arg Arg Ser Gln Arg Ser Glu Glu 195 200 205 Arg Cys ValGlu Ile Pro 210 41 231 PRT Homo sapiens 41 Met Met Pro Lys His Cys PheLeu Gly Phe Leu Ile Ser Phe Phe Leu 1 5 10 15 Thr Gly Val Ala Gly ThrGln Ser Thr His Glu Ser Leu Lys Pro Gln 20 25 30 Arg Val Gln Phe Gln SerArg Asn Phe His Asn Ile Leu Gln Trp Gln 35 40 45 Pro Gly Arg Ala Leu ThrGly Asn Ser Ser Val Tyr Phe Val Gln Tyr 50 55 60 Lys Ile Tyr Gly Gln ArgGln Trp Lys Asn Lys Glu Asp Cys Trp Gly 65 70 75 80 Thr Gln Glu Leu SerCys Asp Leu Thr Ser Glu Thr Ser Asp Ile Gln 85 90 95 Glu Pro Tyr Tyr GlyArg Val Arg Ala Ala Ser Ala Gly Ser Tyr Ser 100 105 110 Glu Trp Ser MetThr Pro Arg Phe Thr Pro Trp Trp Glu Thr Lys Ile 115 120 125 Asp Pro ProVal Met Asn Ile Thr Gln Val Asn Gly Ser Leu Leu Val 130 135 140 Ile LeuHis Ala Pro Asn Leu Pro Tyr Arg Tyr Gln Lys Glu Lys Asn 145 150 155 160Val Ser Ile Glu Asp Tyr Tyr Glu Leu Leu Tyr Arg Val Phe Ile Ile 165 170175 Asn Asn Ser Leu Glu Lys Glu Gln Lys Val Tyr Glu Gly Ala His Arg 180185 190 Ala Val Glu Ile Glu Ala Leu Thr Pro His Ser Ser Tyr Cys Val Val195 200 205 Ala Glu Ile Tyr Gln Pro Met Leu Asp Arg Arg Ser Gln Arg SerGlu 210 215 220 Glu Arg Cys Val Glu Ile Pro 225 230 42 263 PRT Homosapiens 42 Met Met Pro Lys His Cys Phe Leu Gly Phe Leu Ile Ser Phe PheLeu 1 5 10 15 Thr Gly Val Ala Gly Thr Gln Ser Thr His Glu Ser Leu LysPro Gln 20 25 30 Arg Val Gln Phe Gln Ser Arg Asn Phe His Asn Ile Leu GlnTrp Gln 35 40 45 Pro Gly Arg Ala Leu Thr Gly Asn Ser Ser Val Tyr Phe ValGln Tyr 50 55 60 Lys Ile Met Phe Ser Cys Ser Met Lys Ser Ser His Gln LysPro Ser 65 70 75 80 Gly Cys Trp Gln His Ile Ser Cys Asn Phe Pro Gly CysArg Thr Leu 85 90 95 Ala Lys Tyr Gly Gln Arg Gln Trp Lys Asn Lys Glu AspCys Trp Gly 100 105 110 Thr Gln Glu Leu Ser Cys Asp Leu Thr Ser Glu ThrSer Asp Ile Gln 115 120 125 Glu Pro Tyr Tyr Gly Arg Val Arg Ala Ala SerAla Gly Ser Tyr Ser 130 135 140 Glu Trp Ser Met Thr Pro Arg Phe Thr ProTrp Trp Glu Thr Lys Ile 145 150 155 160 Asp Pro Pro Val Met Asn Ile ThrGln Val Asn Gly Ser Leu Leu Val 165 170 175 Ile Leu His Ala Pro Asn LeuPro Tyr Arg Tyr Gln Lys Glu Lys Asn 180 185 190 Val Ser Ile Glu Asp TyrTyr Glu Leu Leu Tyr Arg Val Phe Ile Ile 195 200 205 Asn Asn Ser Leu GluLys Glu Gln Lys Val Tyr Glu Gly Ala His Arg 210 215 220 Ala Val Glu IleGlu Ala Leu Thr Pro His Ser Ser Tyr Cys Val Val 225 230 235 240 Ala GluIle Tyr Gln Pro Met Leu Asp Arg Arg Ser Gln Arg Ser Glu 245 250 255 GluArg Cys Val Glu Ile Pro 260 43 259 PRT Homo sapiens 43 Met Tyr Val LeuSer Pro Val Glu Phe Ile Ile Leu Gln Leu Leu Phe 1 5 10 15 Ile Gln AlaIle Ser Ser Ser Leu Lys Gly Phe Leu Ser Ala Met Arg 20 25 30 Leu Ala HisArg Gly Cys Asn Val Asp Thr Pro Val Ser Thr Leu Thr 35 40 45 Pro Val LysThr Ser Glu Phe Glu Asn Phe Lys Thr Lys Met Val Ile 50 55 60 Thr Ser LysLys Asp Tyr Pro Leu Ser Lys Asn Phe Pro Tyr Ser Leu 65 70 75 80 Glu HisLeu Gln Thr Ser Tyr Cys Gly Leu Val Arg Val Asp Met Arg 85 90 95 Met LeuCys Leu Lys Ser Leu Arg Lys Leu Asp Leu Ser His Asn His 100 105 110 IleLys Lys Leu Pro Ala Thr Ile Gly Asp Leu Ile His Leu Gln Glu 115 120 125Leu Asn Leu Asn Asp Asn His Leu Glu Ser Phe Ser Val Ala Leu Cys 130 135140 His Ser Thr Leu Gln Lys Ser Leu Arg Ser Leu Asp Leu Ser Lys Asn 145150 155 160 Lys Ile Lys Ala Leu Pro Val Gln Phe Cys Gln Leu Gln Glu LeuLys 165 170 175 Asn Leu Lys Leu Asp Asp Asn Glu Leu Ile Gln Phe Pro CysLys Ile 180 185 190 Gly Gln Leu Ile Asn Leu Arg Phe Leu Ser Ala Ala ArgAsn Lys Leu 195 200 205 Pro Phe Leu Pro Ser Glu Phe Arg Asn Leu Ser LeuGlu Tyr Leu Asp 210 215 220 Leu Phe Gly Asn Thr Phe Glu Gln Pro Lys ValLeu Pro Val Ile Lys 225 230 235 240 Leu Gln Ala Pro Leu Thr Leu Leu GluSer Ser Ala Arg Thr Ile Leu 245 250 255 His Asn Arg 44 416 PRT Homosapiens 44 Met Lys Leu His Cys Glu Val Glu Val Ile Ser Arg His Leu ProAla 1 5 10 15 Leu Gly Leu Arg Asn Arg Gly Lys Gly Val Arg Ala Val LeuSer Leu 20 25 30 Cys Gln Gln Thr Ser Arg Ser Gln Pro Pro Val Arg Ala PheLeu Leu 35 40 45 Ile Ser Thr Leu Lys Asp Lys Arg Gly Thr Arg Tyr Glu LeuArg Glu 50 55 60 Asn Ile Glu Gln Phe Phe Thr Lys Phe Val Asp Glu Gly LysAla Thr 65 70 75 80 Val Arg Leu Lys Glu Pro Pro Val Asp Ile Cys Leu SerLys Ala Ile 85 90 95 Ser Ser Ser Leu Lys Gly Phe Leu Ser Ala Met Arg LeuAla His Arg 100 105 110 Gly Cys Asn Val Asp Thr Pro Val Ser Thr Leu ThrPro Val Lys Thr 115 120 125 Ser Glu Phe Glu Asn Phe Lys Thr Lys Met ValIle Thr Ser Lys Lys 130 135 140 Asp Tyr Pro Leu Ser Lys Asn Phe Pro TyrSer Leu Glu His Leu Gln 145 150 155 160 Thr Ser Tyr Cys Gly Leu Val ArgVal Asp Met Arg Met Leu Cys Leu 165 170 175 Lys Ser Leu Arg Lys Leu AspLeu Ser His Asn His Ile Lys Lys Leu 180 185 190 Pro Ala Thr Ile Gly AspLeu Ile His Leu Gln Glu Leu Asn Leu Asn 195 200 205 Asp Asn His Leu GluSer Phe Ser Val Ala Leu Cys His Ser Thr Leu 210 215 220 Gln Lys Ser LeuArg Ser Leu Asp Leu Ser Lys Asn Lys Ile Lys Ala 225 230 235 240 Leu ProVal Gln Phe Cys Gln Leu Gln Glu Leu Lys Asn Leu Lys Leu 245 250 255 AspAsp Asn Glu Leu Ile Gln Phe Pro Cys Lys Ile Gly Gln Leu Ile 260 265 270Asn Leu Arg Phe Leu Ser Ala Ala Arg Asn Lys Leu Pro Phe Leu Pro 275 280285 Ser Glu Phe Arg Asn Leu Ser Leu Glu Tyr Leu Asp Leu Phe Gly Asn 290295 300 Thr Phe Glu Gln Pro Lys Val Leu Pro Val Ile Lys Leu Gln Ala Pro305 310 315 320 Leu Thr Leu Leu Glu Ser Ser Ala Arg Thr Ile Leu His AsnArg Asn 325 330 335 Arg Ile Pro Tyr Gly Ser His Ile Ile Pro Phe His LeuCys Gln Asp 340 345 350 Leu Asp Thr Ala Lys Ile Cys Val Cys Gly Arg PheCys Leu Asn Ser 355 360 365 Phe Ile Gln Gly Thr Thr Thr Met Asn Leu HisSer Val Ala His Thr 370 375 380 Val Val Leu Val Asp Asn Leu Gly Gly ThrGlu Ala Pro Ile Ile Ser 385 390 395 400 Tyr Phe Cys Ser Leu Gly Cys TyrVal Asn Ser Ser Asp Met Leu Lys 405 410 415

What is claimed is:
 1. An isolated polypeptide selected from the groupconsisting of: (a) an isolated polypeptide encoded by a polynucleotidecomprising a sequence set forth in Table I; (b) an isolated polypeptidecomprising a polypeptide sequence set forth in Table I; and (c) apolypeptide sequence of a gene set forth in Table I.
 2. An isolatedpolynucleotide selected from the group consisting of: (a) an isolatedpolynucleotide comprising a polynucleotide sequence set forth in TableI; (b) an isolated polynucleotide of a gene set forth in Table I; (c) anisolated polynucleotide comprising a polynucleotide sequence encoding apolypeptide set forth in Table I; (d) an isolated polynucleotideencoding a polypeptide set forth in Table I; (e) a polynucleotide whichis an RNA equivalent of the polynucleotide of (a) to (d); or apolynucleotide sequence complementary to said isolated polynucleotide.3. An expression vector comprising a polynucleotide capable of producinga polypeptide of claim 1 when said expression vector is present in acompatible host cell.
 4. A process for producing a recombinant host cellwhich comprises the step of introducing an expression vector comprisinga polynucleotide capable of producing a polypeptide of claim 1 into acell such that the host cell, under appropriate culture conditions,produces said polypeptide.
 5. A recombinant host cell produced by theprocess of claim
 4. 6. A membrane of a recombinant host cell of claim 5expressing said polypeptide.
 7. A process for producing a polypeptidewhich comprises culturing a host cell of claim 5 under conditionssufficient for the production of said polypeptide and recovering saidpolypeptide from the culture.